Ignet
Search (e.g., vaccine, IFNG): Help
About
Home
Introduction
Statistics
Programs
Dignet
Gene
GenePair
BioSummarAI
Help & Docs
Documents
Help
FAQs
Links
Acknowledge
Disclaimer
Contact Us
UM Logo

UMMS Logo

UMMS Logo

Gene Information

Gene symbol: HLA-A

Gene name: major histocompatibility complex, class I, A

HGNC ID: 4931

Related Genes

# Gene Symbol Number of hits
1 AAVS1 1 hits
2 ABO 1 hits
3 ACE 1 hits
4 ACPP 1 hits
5 ACTG1 1 hits
6 ADAM17 1 hits
7 ADCY10 1 hits
8 ADFP 1 hits
9 AFP 1 hits
10 ALCAM 1 hits
11 APC 1 hits
12 APOBEC3G 1 hits
13 APOE 1 hits
14 ASPH 1 hits
15 ATP2C1 1 hits
16 ATP6AP1 1 hits
17 ATP6V1E1 1 hits
18 B2M 1 hits
19 BAGE 1 hits
20 BCL2 1 hits
21 BCR 1 hits
22 BIRC5 1 hits
23 BIRC7 1 hits
24 BOLA1 1 hits
25 BOLA2 1 hits
26 BRAP 1 hits
27 BST2 1 hits
28 C19orf10 1 hits
29 C1QB 1 hits
30 C2orf28 1 hits
31 C3 1 hits
32 C4A 1 hits
33 C4B 1 hits
34 C8orf4 1 hits
35 CALR 1 hits
36 CAP1 1 hits
37 CCL19 1 hits
38 CCL2 1 hits
39 CCL3 1 hits
40 CCL4 1 hits
41 CCL5 1 hits
42 CCL7 1 hits
43 CCR1 1 hits
44 CCR2 1 hits
45 CCR5 1 hits
46 CCR7 1 hits
47 CD14 1 hits
48 CD19 1 hits
49 CD1A 1 hits
50 CD1B 1 hits
51 CD1C 1 hits
52 CD1D 1 hits
53 CD2 1 hits
54 CD209 1 hits
55 CD247 1 hits
56 CD27 1 hits
57 CD274 1 hits
58 CD28 1 hits
59 CD33 1 hits
60 CD34 1 hits
61 CD38 1 hits
62 CD4 1 hits
63 CD40 1 hits
64 CD40LG 1 hits
65 CD44 1 hits
66 CD48 1 hits
67 CD5 1 hits
68 CD58 1 hits
69 CD6 1 hits
70 CD63 1 hits
71 CD68 1 hits
72 CD69 1 hits
73 CD70 1 hits
74 CD79A 1 hits
75 CD80 1 hits
76 CD81 1 hits
77 CD83 1 hits
78 CD86 1 hits
79 CD8A 1 hits
80 CD9 1 hits
81 CD93 1 hits
82 CD97 1 hits
83 CDKN1A 1 hits
84 CEACAM5 1 hits
85 CHAF1A 1 hits
86 CIITA 1 hits
87 CLDN11 1 hits
88 CLIP1 1 hits
89 CNOT7 1 hits
90 COL1A1 1 hits
91 CPAT1 1 hits
92 CPN1 1 hits
93 CR2 1 hits
94 CRP 1 hits
95 CSF1 1 hits
96 CSF2 1 hits
97 CTAG1B 1 hits
98 CTLA4 1 hits
99 CTS1 1 hits
100 CTSB 1 hits
101 CXADR 1 hits
102 CXCL10 1 hits
103 CXCL2 1 hits
104 CXCR4 1 hits
105 CYCS 1 hits
106 CYP1B1 1 hits
107 DARC 1 hits
108 DCT 1 hits
109 DDX58 1 hits
110 DNAI1 1 hits
111 DNALI1 1 hits
112 DNMT1 1 hits
113 DPP4 1 hits
114 DR1 1 hits
115 DYNLT1 1 hits
116 EBNA1BP2 1 hits
117 EEA1 1 hits
118 EGFR 1 hits
119 EGR2 1 hits
120 EIF2AK2 1 hits
121 ELA2 1 hits
122 EMR3 1 hits
123 ENPEP 1 hits
124 ENPP3 1 hits
125 EPS8 1 hits
126 ERBB2 1 hits
127 ERVWE1 1 hits
128 FAM48A 1 hits
129 FAM57A 1 hits
130 FANCC 1 hits
131 FAS 1 hits
132 FASLG 1 hits
133 FCAMR 1 hits
134 FCGR1A 1 hits
135 FCGR2A 1 hits
136 FCGR3A 1 hits
137 FCRL6 1 hits
138 FLNB 1 hits
139 FLT1 1 hits
140 FOLH1 1 hits
141 FOLR1 1 hits
142 FOXG1 1 hits
143 FOXP3 1 hits
144 FUT4 1 hits
145 G6PC2 1 hits
146 GABARAPL2 1 hits
147 GAD1 1 hits
148 GINS2 1 hits
149 GLO1 1 hits
150 GP2 1 hits
151 GPA33 1 hits
152 GPC3 1 hits
153 GSTA1 1 hits
154 GZMA 1 hits
155 GZMB 1 hits
156 GZMK 1 hits
157 HABP2 1 hits
158 HDAC9 1 hits
159 HIST2H2AC 1 hits
160 HIST2H2BE 1 hits
161 HLA-B 1 hits
162 HLA-C 1 hits
163 HLA-DMA 1 hits
164 HLA-DOA 1 hits
165 HLA-DOB 1 hits
166 HLA-DPA1 1 hits
167 HLA-DQA1 1 hits
168 HLA-DQB1 1 hits
169 HLA-DRA 1 hits
170 HLA-DRB1 1 hits
171 HLA-DRB4 1 hits
172 HLA-DRB5 1 hits
173 HLA-E 1 hits
174 HLA-G 1 hits
175 HLA-H 1 hits
176 HM13 1 hits
177 HMHA1 1 hits
178 HPSE 1 hits
179 HRAS 1 hits
180 HSD17B12 1 hits
181 HSF1 1 hits
182 HSP90AA1 1 hits
183 HSPA1A 1 hits
184 HSPA1B 1 hits
185 HSPA5 1 hits
186 HSPA8 1 hits
187 HSPB1 1 hits
188 HSPD1 1 hits
189 ICAM1 1 hits
190 ICAM3 1 hits
191 IDH1 1 hits
192 IER3 1 hits
193 IFIH1 1 hits
194 IFNA1 1 hits
195 IFNB1 1 hits
196 IFNG 1 hits
197 IGF2BP3 1 hits
198 IGH 1 hits
199 IGHG3 1 hits
200 IGKV2-18 1 hits
201 IGKV2-23 1 hits
202 IGKV2-24 1 hits
203 IGKV2D-19 1 hits
204 IGKV3D-20 1 hits
205 IGKV6D-21 1 hits
206 IGSF11 1 hits
207 IGSF8 1 hits
208 IL10 1 hits
209 IL12A 1 hits
210 IL12B 1 hits
211 IL13 1 hits
212 IL13RA1 1 hits
213 IL13RA2 1 hits
214 IL15 1 hits
215 IL17D 1 hits
216 IL18 1 hits
217 IL1A 1 hits
218 IL1B 1 hits
219 IL2 1 hits
220 IL2RA 1 hits
221 IL3 1 hits
222 IL4 1 hits
223 IL4R 1 hits
224 IL5 1 hits
225 IL6 1 hits
226 IL7 1 hits
227 IL8 1 hits
228 IL9 1 hits
229 INDO 1 hits
230 INS 1 hits
231 INTS1 1 hits
232 INTU 1 hits
233 IRF1 1 hits
234 ISG20 1 hits
235 ITGAE 1 hits
236 ITGAL 1 hits
237 ITGAM 1 hits
238 ITGAX 1 hits
239 ITGB2 1 hits
240 IV 1 hits
241 JAG1 1 hits
242 JAK2 1 hits
243 KDR 1 hits
244 KIF20A 1 hits
245 KIF2C 1 hits
246 KIR2DL1 1 hits
247 KIR2DL2 1 hits
248 KIR2DL3 1 hits
249 KIR2DL5B 1 hits
250 KIR2DS2 1 hits
251 KIR3DL1 1 hits
252 KLK3 1 hits
253 KLRA1 1 hits
254 KLRC1 1 hits
255 KLRD1 1 hits
256 KLRK1 1 hits
257 KRAS 1 hits
258 LAG3 1 hits
259 LAMP1 1 hits
260 LAMP3 1 hits
261 LCK 1 hits
262 LEFTY2 1 hits
263 LGALS1 1 hits
264 LGALS9 1 hits
265 LGMN 1 hits
266 LMNA 1 hits
267 LTA 1 hits
268 LY6E 1 hits
269 LY6K 1 hits
270 LY75 1 hits
271 MAA 1 hits
272 MAGEA1 1 hits
273 MAGEA10 1 hits
274 MAGEA2 1 hits
275 MAGEA3 1 hits
276 MAGEA4 1 hits
277 MAP1LC3A 1 hits
278 MAP2K1IP1 1 hits
279 MAP3K14 1 hits
280 MAPK1 1 hits
281 MARCH1 1 hits
282 MBP 1 hits
283 MC1R 1 hits
284 MCL1 1 hits
285 MEFV 1 hits
286 MET 1 hits
287 MFI2 1 hits
288 MIB1 1 hits
289 MICA 1 hits
290 MICB 1 hits
291 MIP 1 hits
292 MKI67 1 hits
293 MLANA 1 hits
294 MME 1 hits
295 MOG 1 hits
296 MR1 1 hits
297 MRC1 1 hits
298 MRPL28 1 hits
299 MS4A1 1 hits
300 MUC1 1 hits
301 MUC16 1 hits
302 MUC5AC 1 hits
303 MYCN 1 hits
304 MYD88 1 hits
305 MYH6 1 hits
306 MYO1G 1 hits
307 NCAM1 1 hits
308 NCF1 1 hits
309 NCR1 1 hits
310 NDUFB4 1 hits
311 NEU1 1 hits
312 NFKB1 1 hits
313 NOS2A 1 hits
314 NPPB 1 hits
315 NRSN1 1 hits
316 NUF2 1 hits
317 PAF1 1 hits
318 PAX3 1 hits
319 PCNA 1 hits
320 PDCD1 1 hits
321 PDCD1LG2 1 hits
322 PDIA6 1 hits
323 PDLIM7 1 hits
324 PLA2G1B 1 hits
325 PLAC1 1 hits
326 PLP1 1 hits
327 PMPS 1 hits
328 POLD4 1 hits
329 POLE3 1 hits
330 PRAME 1 hits
331 PRDM1 1 hits
332 PROZ 1 hits
333 PRSS7 1 hits
334 PRTN3 1 hits
335 PSCA 1 hits
336 PSMB8 1 hits
337 PSMB9 1 hits
338 PSMD9 1 hits
339 PTGS2 1 hits
340 PTH 1 hits
341 PTHLH 1 hits
342 PTPN11 1 hits
343 PTPRC 1 hits
344 PTPRN 1 hits
345 PVR 1 hits
346 RAF1 1 hits
347 RANBP2 1 hits
348 RBM45 1 hits
349 RCA1 1 hits
350 RHOC 1 hits
351 RPS27A 1 hits
352 RRM1 1 hits
353 S100A1 1 hits
354 S100B 1 hits
355 SART3 1 hits
356 SCD5 1 hits
357 SCGB2A2 1 hits
358 SCRN1 1 hits
359 SCT 1 hits
360 SEC14L2 1 hits
361 SELPLG 1 hits
362 SERPINA5 1 hits
363 SETBP1 1 hits
364 SILV 1 hits
365 SLA 1 hits
366 SLC11A1 1 hits
367 SLC30A10 1 hits
368 SLC30A8 1 hits
369 SLC44A1 1 hits
370 SLC6A3 1 hits
371 SOCS1 1 hits
372 SOD1 1 hits
373 SOS1 1 hits
374 SOX6 1 hits
375 SP1 1 hits
376 SP2 1 hits
377 SPA17 1 hits
378 SQSTM1 1 hits
379 SSX2 1 hits
380 STAG2 1 hits
381 STAT3 1 hits
382 STX1A 1 hits
383 STX4 1 hits
384 TAC4 1 hits
385 TACSTD1 1 hits
386 TAP1 1 hits
387 TAP2 1 hits
388 TAPBP 1 hits
389 TAT 1 hits
390 TBX1 1 hits
391 TBX21 1 hits
392 TCL1A 1 hits
393 TEK 1 hits
394 TERT 1 hits
395 TG 1 hits
396 TGFA 1 hits
397 TGFB1 1 hits
398 TGFB2 1 hits
399 TH 1 hits
400 TH1L 1 hits
401 TLR2 1 hits
402 TLR3 1 hits
403 TLR4 1 hits
404 TLR7 1 hits
405 TLR9 1 hits
406 TMEM37 1 hits
407 TNF 1 hits
408 TNFAIP3 1 hits
409 TNFRSF10A 1 hits
410 TNFRSF1A 1 hits
411 TNFRSF25 1 hits
412 TNFRSF4 1 hits
413 TNFRSF9 1 hits
414 TP53 1 hits
415 TPBG 1 hits
416 TRA 1 hits
417 TRAF3 1 hits
418 TRB 1 hits
419 TSHR 1 hits
420 TSLP 1 hits
421 TSPAN7 1 hits
422 TTK 1 hits
423 TXNDC15 1 hits
424 TYMS 1 hits
425 TYR 1 hits
426 UPK1B 1 hits
427 VCAM1 1 hits
428 VEGFA 1 hits
429 VHLL 1 hits
430 VSX1 1 hits
431 WARS 1 hits
432 WT1 1 hits
433 WWOX 1 hits
434 XAGE1B 1 hits
435 XRCC1 1 hits
436 ZMYND10 1 hits
437 ZP2 1 hits
438 ZP3 1 hits

Related Sentences

# PMID Sentence
1 344795 BALB.B10 mice carrying the high responder (B10) MHC on the nonresponder (BALB/c) background were not protected.
2 1343352 Data show that T lymphocytes were induced to enhance the expression of class II MHC molecules, whilst a consistent number of CD4+ lymphocytes lost L-selectin, both phenomena indicating an activation status.
3 1343352 OPV administration also modulated important molecules on the membrane of polymorphonuclear leukocytes, namely CD11b and CD16, strongly suggesting an activation of these cells and an enhancement of their defensive capacities.
4 1351088 Production of transmembrane and secreted forms of tumor necrosis factor (TNF)-alpha by HIV-1-specific CD4+ cytolytic T lymphocyte clones.
5 1351088 Candidate AIDS vaccines consisting of recombinant forms of the HIV-1 envelope glycoprotein induce, in seronegative human volunteers, an env-specific T cell response that includes CD4+, MHC class II-restricted CTL capable of lysing HIV-1-infected target cells.
6 1351088 In this study, we have analyzed the production of the cytokines TNF-alpha and lymphotoxin (LT) by a set of env-specific CD4+ human CTL clones.
7 1351088 TNF-alpha and LT are of interest because of their potential role in target cell destruction by CD4+ CTL.
8 1351088 We found that, upon interaction with target cells expressing env epitopes in the context of the appropriate MHC class II molecules, CD4+ CTL released TNF-alpha with kinetics that were rapid, compared with other cytokines, and that were generally similar to the kinetics of target cell destruction.
9 1351088 A novel flow cytometric assay was used to show that physiologic activation of CD4+ CTL with target APC induced expression by the CTL of cell surface forms of TNF-alpha.
10 1351088 For a subset of CD4+ CTL, we found that treatment of CTL with cyclosporin A inhibited Ag-induced production of both transmembrane and secreted forms of TNF-alpha but had no effect on cytolysis.
11 1351088 Thus, although transmembrane and secreted TNF-alpha produced by HIV-1-specific CD4+ CTL may have important effects in vivo, the rapid destruction of target APC by the set of CD4+ CTL clones described here occurs through a TNF-alpha-independent mechanism.
12 1371784 P18 was presented by at least four different class I MHC molecules from independent haplotypes (H-2d, p, u, and q to CD8+ CTL.
13 1371784 HP53 was also presented by the same four different class I MHC molecules to CD8+ CTL although at higher concentrations.
14 1371784 T1 was presented by class I molecules in three different strains of distinct MHC types (B10.M, H-2f; B10.A, H-2a; and B10, H-2b) to CTL.
15 1371784 The CTL specific for P18 and HP53 were shown to be CD8+ and CD4- and to kill targets expressing endogenously synthesized whole gp160 as well as targets pulsed with the corresponding peptide.
16 1371784 P18 was presented by at least four different class I MHC molecules from independent haplotypes (H-2d, p, u, and q to CD8+ CTL.
17 1371784 HP53 was also presented by the same four different class I MHC molecules to CD8+ CTL although at higher concentrations.
18 1371784 T1 was presented by class I molecules in three different strains of distinct MHC types (B10.M, H-2f; B10.A, H-2a; and B10, H-2b) to CTL.
19 1371784 The CTL specific for P18 and HP53 were shown to be CD8+ and CD4- and to kill targets expressing endogenously synthesized whole gp160 as well as targets pulsed with the corresponding peptide.
20 1371784 P18 was presented by at least four different class I MHC molecules from independent haplotypes (H-2d, p, u, and q to CD8+ CTL.
21 1371784 HP53 was also presented by the same four different class I MHC molecules to CD8+ CTL although at higher concentrations.
22 1371784 T1 was presented by class I molecules in three different strains of distinct MHC types (B10.M, H-2f; B10.A, H-2a; and B10, H-2b) to CTL.
23 1371784 The CTL specific for P18 and HP53 were shown to be CD8+ and CD4- and to kill targets expressing endogenously synthesized whole gp160 as well as targets pulsed with the corresponding peptide.
24 1372650 Identification of overlapping HLA class I-restricted cytotoxic T cell epitopes in a conserved region of the human immunodeficiency virus type 1 envelope glycoprotein: definition of minimum epitopes and analysis of the effects of sequence variation.
25 1376366 Our study provides the first evidence that CD8+ CTL can recognize an epitope from the HCV sequence in association with a class I MHC molecule.
26 1460286 By analytic flow cytometry, the mice immunized with PRP-OMPC demonstrated an increase in large splenocytes expressing the Ag Mac-1 (CD11b, CR3).
27 1460286 By immunohistochemical staining, the cells were identified as macrophages due to expression of Mac-1 and p150,95 (CD11C) Ag.
28 1460286 After PRP-OMPC immunization, severe combined immunodeficient mice also demonstrated significant splenomegaly with an increase in macrophages identified by expression of Mac-1 and MHC class II Ag.
29 1460429 In this report, we show that after a single intramuscular vaccination, rhesus monkeys develop a CD8+ cell-mediated, MHC class I-restricted CTL response that recognizes the synthetic peptide immunogen.
30 1460429 These results demonstrate that virus-specific, MHC class I-restricted, CD8+ CTL can be elicited by a safe, nonreplicating viral subunit vaccine in a primate model for acquired immune deficiency syndrome.
31 1460429 In this report, we show that after a single intramuscular vaccination, rhesus monkeys develop a CD8+ cell-mediated, MHC class I-restricted CTL response that recognizes the synthetic peptide immunogen.
32 1460429 These results demonstrate that virus-specific, MHC class I-restricted, CD8+ CTL can be elicited by a safe, nonreplicating viral subunit vaccine in a primate model for acquired immune deficiency syndrome.
33 1518813 Thus, cationic lipids may facilitate induction of CD8+ T-cell responses in vaccinations with recombinant antigens, and they may serve as readily available reagents for dissecting class I MHC immunity to viruses and other intracellular pathogens.
34 1560752 Antigen-specific T lymphocytes were stimulated by CJ11 cells to proliferate and release interleukins (IL-2 and IL-3).
35 1560752 Thus, production of ML65hsp within the host cytoplasm resulted in association of the antigen with both MHC class I and MHC class II antigen-presenting structures and evoked both lymphocyte proliferation and cytotoxicity towards the antigen-presenting cell.
36 1689366 We have observed that a peptide corresponding to an immunodominant epitope of the HIV-1 envelope protein recognized by class I MHC-restricted CD8+ CTL can also induce T cell help for itself.
37 1689366 The help is necessary for restimulation of CTL precursors in vitro with peptide alone in the absence of exogenous lymphokines, can be removed by depletion of CD4+ T cells, and can be replaced by exogenous IL-2.
38 1689366 Spleen cells of immune B10.A mice behave like CD4-depleted BALB/c spleen cells in that they cannot be restimulated in vitro by the peptide alone, but can with peptide plus IL-2.
39 1691512 Myelin basic protein, MHC restriction molecules and T cell repertoire.
40 1704397 Six epitopes reacting with human cytotoxic CD8+ T cells in the central region of the HIV-1 NEF protein.
41 1704397 Six different epitopes were identified and several points were remarkable: 1) They were all located in two regions of the central part of the NEF protein corresponding to residues 73 to 94 and 113 to 147, respectively. 2) The CTL issued from a single donor could recognize several peptides of the NEF protein. 3) Some of these peptides could be recognized in association with at least two or three different HLA class I molecules. 4) Two different overlapping epitopes were present in a relatively short sequence of 15 amino acids.
42 1709586 The data suggest that the highly repetitive nature of the mucin allows cross-linking of the T-cell receptor on mucin-specific T-cells and therefore accounts for the lack of MHC restriction seen in this system.
43 1711081 Definition of an epitope and MHC class I molecule recognized by gag-specific cytotoxic T lymphocytes in SIVmac-infected rhesus monkeys.
44 1711081 In our report we demonstrate that a particular MHC class I molecule involved in the rhesus monkey's effector T lymphocyte response to SIVmac is expressed at a high frequency in a colony of rhesus monkeys.
45 1711081 SIVmac-infected monkeys that express this MHC class I molecule all develop CTL that are restricted by that molecule and recognize an identical nine amino acid epitope of the SIVmac gag protein.
46 1711081 This MHC class I molecule has been defined as an HLA-A homolog by cDNA cloning and sequencing.
47 1711081 Definition of an epitope and MHC class I molecule recognized by gag-specific cytotoxic T lymphocytes in SIVmac-infected rhesus monkeys.
48 1711081 In our report we demonstrate that a particular MHC class I molecule involved in the rhesus monkey's effector T lymphocyte response to SIVmac is expressed at a high frequency in a colony of rhesus monkeys.
49 1711081 SIVmac-infected monkeys that express this MHC class I molecule all develop CTL that are restricted by that molecule and recognize an identical nine amino acid epitope of the SIVmac gag protein.
50 1711081 This MHC class I molecule has been defined as an HLA-A homolog by cDNA cloning and sequencing.
51 1711081 Definition of an epitope and MHC class I molecule recognized by gag-specific cytotoxic T lymphocytes in SIVmac-infected rhesus monkeys.
52 1711081 In our report we demonstrate that a particular MHC class I molecule involved in the rhesus monkey's effector T lymphocyte response to SIVmac is expressed at a high frequency in a colony of rhesus monkeys.
53 1711081 SIVmac-infected monkeys that express this MHC class I molecule all develop CTL that are restricted by that molecule and recognize an identical nine amino acid epitope of the SIVmac gag protein.
54 1711081 This MHC class I molecule has been defined as an HLA-A homolog by cDNA cloning and sequencing.
55 1711081 Definition of an epitope and MHC class I molecule recognized by gag-specific cytotoxic T lymphocytes in SIVmac-infected rhesus monkeys.
56 1711081 In our report we demonstrate that a particular MHC class I molecule involved in the rhesus monkey's effector T lymphocyte response to SIVmac is expressed at a high frequency in a colony of rhesus monkeys.
57 1711081 SIVmac-infected monkeys that express this MHC class I molecule all develop CTL that are restricted by that molecule and recognize an identical nine amino acid epitope of the SIVmac gag protein.
58 1711081 This MHC class I molecule has been defined as an HLA-A homolog by cDNA cloning and sequencing.
59 1712811 The physical association of HLA class I or H-2 molecules with 36 HIV-1 Nef synthetic peptides was studied using a direct peptide binding assay (PBA) in solid phase.
60 1712811 The PBA results showed that seven partly overlapping regions of the Nef protein contained MHC binding peptides (4-18, 46-67, 73-94, 100-128, 126-155, 182-198, and 192-206).
61 1712811 The two other regions, 4-18 and 46-67, are not yet described as antigenic for human CD8+ cells but they are located in the N-terminal part of Nef that was previously described as being stimulator for rat or chimpanzee CD4+ cells.
62 1712811 The physical association of HLA class I or H-2 molecules with 36 HIV-1 Nef synthetic peptides was studied using a direct peptide binding assay (PBA) in solid phase.
63 1712811 The PBA results showed that seven partly overlapping regions of the Nef protein contained MHC binding peptides (4-18, 46-67, 73-94, 100-128, 126-155, 182-198, and 192-206).
64 1712811 The two other regions, 4-18 and 46-67, are not yet described as antigenic for human CD8+ cells but they are located in the N-terminal part of Nef that was previously described as being stimulator for rat or chimpanzee CD4+ cells.
65 1719081 We have examined the induction and epitope specificity of T cells for the simian immunodeficiency virus (SIV) gag p27 protein in macaques immunized with either a recombinant SIV gag protein or an inactivated SIV vaccine.
66 1719081 CD4+ MHC class II-restricted T cell lines and clones derived from five immunized macaques recognized a total of seven peptides in three immunodominant regions of p27.
67 1719081 Although this epitope is in a conserved region of the gag protein of SIV, its recognition by a CD4+ T cell clone was abrogated by sequence variation in the equivalent HIV protein.
68 1733629 Thus it is only antigen-specific responses involving the T cell receptor pathways and CD4/MHC class II interaction that appear to be inhibited by HIV-1 and gp120.
69 1779176 Both CD4+ and CD8+ CTL have been cloned from the blood of immunized patients.
70 1779176 Many CD4+ clones killed HLA Class II-negative melanomas, and we were able to block cytotoxicity of a particular clone with either anti-HLA Class I or anti-Class II MHC monoclonal antibodies, or both.
71 1828389 We investigated the cellular composition and the major histocompatibility complex (MHC) class II antigen expression in the draining lymph node and the tumour during potentiation of the immune response by intralesional bacillus Calmette-Guérin (BCG) administration in the line 10 hepatocellular carcinoma in the strain 2 guinea-pig.
72 1828389 Taking into account this nine-fold increase, intralesional treatment of BCG increased considerably the number of T helper/inducer (anti-CT7) and T suppressor/cytotoxic (anti-CT6) lymph node cells expressing MHC class II antigen.
73 1828389 The percentage of tumour-infiltrating T cells expressing MHC class II antigen in the tumour was higher than the percentage of T cells in the regional draining lymph node of non-treated guinea-pigs, indicating the presence of activated T cells in the tumour.
74 1828389 In conclusion, with the use of two-colour flow cytofluorometry we have shown that the potentiation of the already existing immune response to line 10 is accompanied by a considerable increase in T helper/inducer, T suppressor/cytotoxic cells and MHC class II antigen in the regional lymph node.
75 1828389 We investigated the cellular composition and the major histocompatibility complex (MHC) class II antigen expression in the draining lymph node and the tumour during potentiation of the immune response by intralesional bacillus Calmette-Guérin (BCG) administration in the line 10 hepatocellular carcinoma in the strain 2 guinea-pig.
76 1828389 Taking into account this nine-fold increase, intralesional treatment of BCG increased considerably the number of T helper/inducer (anti-CT7) and T suppressor/cytotoxic (anti-CT6) lymph node cells expressing MHC class II antigen.
77 1828389 The percentage of tumour-infiltrating T cells expressing MHC class II antigen in the tumour was higher than the percentage of T cells in the regional draining lymph node of non-treated guinea-pigs, indicating the presence of activated T cells in the tumour.
78 1828389 In conclusion, with the use of two-colour flow cytofluorometry we have shown that the potentiation of the already existing immune response to line 10 is accompanied by a considerable increase in T helper/inducer, T suppressor/cytotoxic cells and MHC class II antigen in the regional lymph node.
79 1828389 We investigated the cellular composition and the major histocompatibility complex (MHC) class II antigen expression in the draining lymph node and the tumour during potentiation of the immune response by intralesional bacillus Calmette-Guérin (BCG) administration in the line 10 hepatocellular carcinoma in the strain 2 guinea-pig.
80 1828389 Taking into account this nine-fold increase, intralesional treatment of BCG increased considerably the number of T helper/inducer (anti-CT7) and T suppressor/cytotoxic (anti-CT6) lymph node cells expressing MHC class II antigen.
81 1828389 The percentage of tumour-infiltrating T cells expressing MHC class II antigen in the tumour was higher than the percentage of T cells in the regional draining lymph node of non-treated guinea-pigs, indicating the presence of activated T cells in the tumour.
82 1828389 In conclusion, with the use of two-colour flow cytofluorometry we have shown that the potentiation of the already existing immune response to line 10 is accompanied by a considerable increase in T helper/inducer, T suppressor/cytotoxic cells and MHC class II antigen in the regional lymph node.
83 1828389 We investigated the cellular composition and the major histocompatibility complex (MHC) class II antigen expression in the draining lymph node and the tumour during potentiation of the immune response by intralesional bacillus Calmette-Guérin (BCG) administration in the line 10 hepatocellular carcinoma in the strain 2 guinea-pig.
84 1828389 Taking into account this nine-fold increase, intralesional treatment of BCG increased considerably the number of T helper/inducer (anti-CT7) and T suppressor/cytotoxic (anti-CT6) lymph node cells expressing MHC class II antigen.
85 1828389 The percentage of tumour-infiltrating T cells expressing MHC class II antigen in the tumour was higher than the percentage of T cells in the regional draining lymph node of non-treated guinea-pigs, indicating the presence of activated T cells in the tumour.
86 1828389 In conclusion, with the use of two-colour flow cytofluorometry we have shown that the potentiation of the already existing immune response to line 10 is accompanied by a considerable increase in T helper/inducer, T suppressor/cytotoxic cells and MHC class II antigen in the regional lymph node.
87 1834737 Characterization of streptococcal antigen-specific CD8+, MHC class I-restricted, T cell clones that down-regulate in vitro antibody synthesis.
88 1834737 The function of the CD8+ cloned cells was examined in vitro for their effect on antibody synthesis by Ag-stimulated CD4+ cells and B cells from immunized animals.
89 1834737 Indeed, four of the five clones suppressed SAI/II-specific IgG antibody synthesis when activated with SAI/II and the appropriate MHC-matched APC.
90 1834737 Characterization of streptococcal antigen-specific CD8+, MHC class I-restricted, T cell clones that down-regulate in vitro antibody synthesis.
91 1834737 The function of the CD8+ cloned cells was examined in vitro for their effect on antibody synthesis by Ag-stimulated CD4+ cells and B cells from immunized animals.
92 1834737 Indeed, four of the five clones suppressed SAI/II-specific IgG antibody synthesis when activated with SAI/II and the appropriate MHC-matched APC.
93 1901883 In Leishmania major infections, cure vs progressive disease correlates with the expansion of Th1-like or Th2-like CD4+ populations, respectively.
94 1901883 Splenic lymphocytes from infected Lsh congenic C57BL/10 (Lshs;H-2b) and B10.L-Lshr (Lshr;H-2b) mice and MHC congenic non-curing B10.D2/n (Lshs;H-2d) mice were examined for the production of cytokines representative of these CD4+ populations (IL-2, IL-3, IL-4, IL-5, and IFN-gamma).
95 1901883 In the non-curing B10.D2/n strain, late phase of infection was associated with the decreased ability to produce cytokines in response to Ag and not with the production of IL-4 or IL-5 in response to Ag or mitogen.
96 1901883 Together, these data suggest that over-expansion of Th2-type cells and production of their specific cytokines (IL-4 and IL-5) is not a contributing factor to the variable long term course of L. donovani infection in these strains of mice.
97 1904363 Vaccination of class I major histocompatibility complex (MHC)-restricted murine CD8+ cytotoxic T lymphocytes towards soluble antigens: immunostimulating-ovalbumin complexes enter the class I MHC-restricted antigen pathway and allow sensitization against the immunodominant peptide.
98 1904363 The effector cells induced were MHC restricted, specific for the immunodominant peptide of OVA (258-276), and expressed the CD8+ CD4- phenotype.
99 1904363 These results suggest that ISCOM-based vaccines may be useful to direct hydrophilic soluble antigens into the MHC class I presentation pathway in order to vaccinate CD8+ T lymphocytes.
100 1904363 Vaccination of class I major histocompatibility complex (MHC)-restricted murine CD8+ cytotoxic T lymphocytes towards soluble antigens: immunostimulating-ovalbumin complexes enter the class I MHC-restricted antigen pathway and allow sensitization against the immunodominant peptide.
101 1904363 The effector cells induced were MHC restricted, specific for the immunodominant peptide of OVA (258-276), and expressed the CD8+ CD4- phenotype.
102 1904363 These results suggest that ISCOM-based vaccines may be useful to direct hydrophilic soluble antigens into the MHC class I presentation pathway in order to vaccinate CD8+ T lymphocytes.
103 1904363 Vaccination of class I major histocompatibility complex (MHC)-restricted murine CD8+ cytotoxic T lymphocytes towards soluble antigens: immunostimulating-ovalbumin complexes enter the class I MHC-restricted antigen pathway and allow sensitization against the immunodominant peptide.
104 1904363 The effector cells induced were MHC restricted, specific for the immunodominant peptide of OVA (258-276), and expressed the CD8+ CD4- phenotype.
105 1904363 These results suggest that ISCOM-based vaccines may be useful to direct hydrophilic soluble antigens into the MHC class I presentation pathway in order to vaccinate CD8+ T lymphocytes.
106 1918963 Depletion of CD8+ cells from the splenic effector cell population, however, abrogated the cytotoxic activity, whereas depletion of CD4+ cells had little effect.
107 1918963 Together, these results establish MHC-restricted cytolysis as a major parameter of CD8+ effector function against T. gondii and indicate that, in the case of this protozoan, Ag presentation to CD8+ lymphocytes can occur as a result of either processing within infected cells or exogenous uptake of parasite Ag.
108 1963114 At this time the MHC class II antigen expression of these cells was increased from 21%-32% in the naive controls to 39%-53% in animals with BCG-treated tumors.
109 1975119 Previous reports have demonstrated that the introduction of virus (MCMV, HSV-1) concurrent with a graft-versus-host reaction (GvHR) limited to a class I MHC disparity can result in the enhancement of GvHR-associated phenotypic (changes in CD4/CD8 ratio) and functional (inability to produce secondary antibody responses) alterations including the augmentation of in situ natural killer (NK) and donor anti-host cytotoxic T-cell activity.
110 2110213 Different patterns of the expression of MHC class II Ag on T cells, B cells, and monocytes during the course of immunization with protein or polysaccharide Ag were observed: whereas protein Ag induced a high frequency of HLA-DP- and HLA-DR-expressing cells early in the course of immunization, polysaccharide vaccines elicited low and protracted increases of HLA-DP+ T cells.
111 2147200 CD8+, MHC class I-restricted, env-specific CTL were cloned from PBL of SIVmac-infected monkeys, indicating that such cells constitute a component of the env-specific effector lymphocyte response.
112 2147200 Using this assay we demonstrate that SIVmac env-specific effector lymphocytes are comprised of both CD16-, MHC class I-restricted and CD16+, MHC class I-unrestricted cells.
113 2147200 CD8+, MHC class I-restricted, env-specific CTL were cloned from PBL of SIVmac-infected monkeys, indicating that such cells constitute a component of the env-specific effector lymphocyte response.
114 2147200 Using this assay we demonstrate that SIVmac env-specific effector lymphocytes are comprised of both CD16-, MHC class I-restricted and CD16+, MHC class I-unrestricted cells.
115 2168340 CD4+ virus-specific T cells capable of proliferation were readily induced and, in some circumstances, class II major histocompatibility complex (MHC)-restricted cytotoxicity was detected.
116 2168340 Mice immunized orally with the nucleoprotein-expressing bacteria mounted a strong anti-viral antibody response and spleen cells from such mice proliferated specifically to virus challenge in vitro, producing interferon-gamma (IFN-gamma) and interleukin-2 (IL-2).
117 2184369 Induction of CD8+ cytotoxic T cells by immunization with purified HIV-1 envelope protein in ISCOMs.
118 2184369 However, although most non-living intact protein preparations induce antibodies and CD4+ major histocompatibility complex (MHC) class II-restricted helper and/or cytotoxic T lymphocytes (CTL), they do not elicit CD8+ MHC class I restricted CTL.
119 2184369 We show here that a single subcutaneous immunization in mice with immunostimulating complexes containing either purified intact gp160 envelope glycoprotein of the human immunodeficiency virus (HIV)-1 or influenza haemagglutinin results in reproducible and long-lasting priming of HIV specific or influenza-specific CD8+, MHC class I restricted CTL.
120 2184369 Induction of CD8+ cytotoxic T cells by immunization with purified HIV-1 envelope protein in ISCOMs.
121 2184369 However, although most non-living intact protein preparations induce antibodies and CD4+ major histocompatibility complex (MHC) class II-restricted helper and/or cytotoxic T lymphocytes (CTL), they do not elicit CD8+ MHC class I restricted CTL.
122 2184369 We show here that a single subcutaneous immunization in mice with immunostimulating complexes containing either purified intact gp160 envelope glycoprotein of the human immunodeficiency virus (HIV)-1 or influenza haemagglutinin results in reproducible and long-lasting priming of HIV specific or influenza-specific CD8+, MHC class I restricted CTL.
123 2191918 The infectivity of the human immunodeficiency virus (HIV) is related to the structure of its envelope protein, gp160, which is responsible for viral entry.
124 2191918 We considered the possibility that a structural homology between gp160 and major histocompatibility complex (MHC) molecules might be associated with the extraordinary affinity that gp120 has for its receptor, CD4.
125 2452443 The facts that CTL responses were detected in the context of only one of four class I MHC molecules tested and that the response was limited predominantly to a single epitope indicate that the CTL repertoire elicited by the HIV envelope protein in association with murine class I MHC molecules may be very limited.
126 2458387 Although the clone had the phenotype CD3+CD4+CD8+, proliferation to antigen was blocked by anti-CD8 and anti-HLA-A, B, C, but not by anti-CD4, suggesting that CD4 was not functionally associated with the T cell receptor.
127 2460873 Although the effector cells were predominantly CD8+, both MHC-matched and -unmatched target cells were lysed.
128 2481593 An antigenic peptide of the HIV-1 NEF protein recognized by cytotoxic T lymphocytes of seropositive individuals in association with different HLA-B molecules.
129 2481593 In two different donors, we identified a unique peptide in the NEF protein that could be recognized in association with two different HLA class I molecules.
130 2484961 Here, we use 44 peptides, including ones predicted and not predicted on the basis of amphipathicity to be potential T cell sites, to locate T cell antigenic determinants recognized by mice of four MHC haplotypes immunized with the whole gp 160 envelope protein.
131 2485085 Identification of the main immunogenic region of retinal S-antigen: subordinate influence of MHC, IGH, species or strain differences on the specificity of the antibody response.
132 2493675 We made use of a recombinant vaccinia virus encoding and expressing the murine IL-2 gene and recombinant IL-2 to test the role of IL-2 in the expression of major histocompatibility complex (MHC) class I determined immune response (Ir) gene defects in the response to vaccinia virus.
133 2567317 These T cells could potentially participate in a secondary immune response because they were shown to recognize TT presented by recipient fibroblasts induced to express class II MHC molecules following treatment with IFN-gamma.
134 2574188 The earliest TH defect is the loss of responses to FLU and TET, indicating a selective defect in CD4+ MHC self-restricted TH function.
135 2574188 The later loss of ALLO and PHA IL-2 responses suggests more severe TH dysfunction involving both CD4+ and CD8+ T cells.
136 2680926 In vitro studies have revealed the existence of T-suppressor cells of the phenotype CD8+, CD3+, HLA-DR+, FcR+, 9.3-, which are restricted by major histocompatibility complex (MHC) class II antigens.
137 2943202 Tests for HLA-A, B, C, and DR; for complement proteins C2, C4A, C4B, and BF; and for the erythrocyte enzyme glyoxalase I were done in 17 nonresponders and 3 hyporesponders.
138 2943202 At least one of two extended haplotypes (B44, DR7, FC31 or B8, DR3, SCO1) were detected in 6 of the 9 who did not respond to revaccination, compared with 2 of 11 who responded to a second course of vaccine.
139 3074285 Immune regulatory derangements include lymphokine-induced aberrant expression of MHC Class II molecules on synovial tissues, the presence of a 'resistant' subset of B cells (CD5 + ve), failure of anti-idiotypic control of autoantibodies (not well established as yet in rheumatoid arthritis), and defective immune suppression, revealed by low counts in synovial fluids of a suppressor-inducer subset of CD4 + ve T cells.
140 3074285 The many possibilities for therapeutic immune intervention would include polyclonal or monoclonal antibody to block (a) receptors for antigen on B or T lymphocytes (but this would require knowledge of the rheumatoid arthritis-inducing antigen), (b) the CD4 complex on helper T lymphocytes, (c) MHC Class II (Ia) molecules, for which there are excellent prototypes in experimental immunopathology, or (d) lymphokines or their receptors.
141 3074285 Immune regulatory derangements include lymphokine-induced aberrant expression of MHC Class II molecules on synovial tissues, the presence of a 'resistant' subset of B cells (CD5 + ve), failure of anti-idiotypic control of autoantibodies (not well established as yet in rheumatoid arthritis), and defective immune suppression, revealed by low counts in synovial fluids of a suppressor-inducer subset of CD4 + ve T cells.
142 3074285 The many possibilities for therapeutic immune intervention would include polyclonal or monoclonal antibody to block (a) receptors for antigen on B or T lymphocytes (but this would require knowledge of the rheumatoid arthritis-inducing antigen), (b) the CD4 complex on helper T lymphocytes, (c) MHC Class II (Ia) molecules, for which there are excellent prototypes in experimental immunopathology, or (d) lymphokines or their receptors.
143 3141552 These results indicate that proliferative T cells recognize a limited number of epitopes on F-MuLV envelope protein in the context of I-Ab, hybrid I-Ak/b, and/or hybrid I-Ek/b class II MHC molecules but fail to recognize the same envelope protein in the context of I-Ak or I-Ek molecules.
144 3263440 Proliferation was inhibited by mAb to CD4 and class II MHC gene products.
145 3263440 These CTL were CD4+ and restricted to class II MHC gene products.
146 3263440 Proliferation was inhibited by mAb to CD4 and class II MHC gene products.
147 3263440 These CTL were CD4+ and restricted to class II MHC gene products.
148 3484491 We have shown that human dermal fibroblasts, exposed to interferon-gamma (IFN-gamma) to induce surface class II major histocompatibility complex (MHC) antigens, were capable of presenting tetanus toxoid (TT) antigen to human TT-specific T cell clones.
149 3484491 In addition, the failure of antigen presentation by fibroblasts to resting T cells was reversed by the addition of recombinant human interleukin 2 (rIL 2) to cultures, but not of purified human interleukin 1 (IL 1).
150 3487504 B10.A(5R) mice bearing nonresponder MHC class I antigen in the D and K regions show no anti-NP Tc responses, however they do show a strong A-virus cross-reactive anti-influenza cytotoxicity.
151 6808699 Several genetic markers, HLA-A, B and DR antigens, Gm and Km types, and ABO blood types, were studied on 78 rubella seronegative schoolgirls immunized with "TO336" rubella vaccine.
152 7489749 We, therefore, generated DC from peripheral blood of normal donors in the presence of granulocyte/macrophage colony-stimulating factor and interleukin-4.
153 7489749 Flow cytometric analysis of the cells during a 2-week culture revealed a loss of CD14 and CD34 expression, a concomittent increase of CD1a, CD11a,b and c, CD44, CD45, CD54, HLA-class I and II, and intermediate levels of CD26, CD80 and CD86.
154 7494256 Short-term CD4+ T-cell lines were derived by using full-length HAs of virus A/Beijing/32/92 from 12 unrelated, major histocompatibility complex (MHC) class I and II haplotyped adults with a history of influenza in November and December 1993 and from 6 adults with no history of influenza during the preceding 4 years but who responded to HA.
155 7494256 Our study included one pair of unrelated donors expressing identical HLA DRB1 and DQB1 alleles and two pairs of donors sharing low-resolution MHC class II types.
156 7494256 Short-term CD4+ T-cell lines were derived by using full-length HAs of virus A/Beijing/32/92 from 12 unrelated, major histocompatibility complex (MHC) class I and II haplotyped adults with a history of influenza in November and December 1993 and from 6 adults with no history of influenza during the preceding 4 years but who responded to HA.
157 7494256 Our study included one pair of unrelated donors expressing identical HLA DRB1 and DQB1 alleles and two pairs of donors sharing low-resolution MHC class II types.
158 7495519 Such genes include the murine MHC class I gene, Ld (toxoplasmosis), HLA-BW53, HLA DRB1* 1302-DQ B10s01 and TNF2 (malaria), murine Nramp (toxoplasmosis, leishmaniasis and tuberculosis), gene(s) modulating the T-helper type 1 and type 2 dichotomy (leishmaniasis, leprosy and HIV infection) and the natural killer cell complex (cytomegalovirus infection).
159 7500019 While several approaches have succeeded in identifying major histocompatibility complex (MHC) class I bound peptides that stimulate CD8+ T cells, these approaches have been difficult to extend to peptides presented by MHC class II molecules that stimulate CD4+ T cells.
160 7511396 In the classic model of antigen processing and presentation, viral antigens must be synthesized within the cytoplasm of infected cells to be processed and presented to CD8+, MHC class I-restricted cytotoxic T lymphocytes (CTLs).
161 7513904 Many tumors express tumor-specific antigens capable of being presented to CD8+ T cells by major histocompatibility complex (MHC) class I molecules.
162 7516671 CD4+ T lymphocytes recognize peptide fragments of antigens that lie in the antigen binding pocket of class II major histocompatibility complex (MHC) molecules expressed on antigen-presenting cells.
163 7517870 Immunization with recombinant vaccinia expressing the full length PfSSP2 induced antigen specific, MHC-restricted, CD8+ T cell-dependent cytolytic activity against these two peptides.
164 7521921 We also employed one-dimensional isoelectric focusing to characterize the MHC class I molecule of the rhesus monkey that binds this SIVmac envelope peptide fragment.
165 7521921 Cloning and sequencing the cDNA encoding this rhesus monkey MHC class I molecule demonstrates that it is a newly described HLA-A homolog, Mamu-A*02.
166 7521921 This viral CTL epitope and its restricting MHC class I molecule will facilitate the use of the SIVmac rhesus monkey model for studies of envelope-based vaccine strategies and for exploring AIDS immunopathogenesis.
167 7521921 We also employed one-dimensional isoelectric focusing to characterize the MHC class I molecule of the rhesus monkey that binds this SIVmac envelope peptide fragment.
168 7521921 Cloning and sequencing the cDNA encoding this rhesus monkey MHC class I molecule demonstrates that it is a newly described HLA-A homolog, Mamu-A*02.
169 7521921 This viral CTL epitope and its restricting MHC class I molecule will facilitate the use of the SIVmac rhesus monkey model for studies of envelope-based vaccine strategies and for exploring AIDS immunopathogenesis.
170 7521921 We also employed one-dimensional isoelectric focusing to characterize the MHC class I molecule of the rhesus monkey that binds this SIVmac envelope peptide fragment.
171 7521921 Cloning and sequencing the cDNA encoding this rhesus monkey MHC class I molecule demonstrates that it is a newly described HLA-A homolog, Mamu-A*02.
172 7521921 This viral CTL epitope and its restricting MHC class I molecule will facilitate the use of the SIVmac rhesus monkey model for studies of envelope-based vaccine strategies and for exploring AIDS immunopathogenesis.
173 7523139 Priming of CD8+ cytotoxic T lymphocyte (CTL) responses with recombinant proteins has been facilitated by the development of novel adjuvants that deliver antigens into the class I major histocompatibility complex (MHC) pathway.
174 7523139 Envelope-specific CD8+ T lymphocytes were detected in BALB/c mice immunized with env 2-3, a 55-kDa yeast-derived envelope protein that is not glycosylated and lacks a native conformation.
175 7527447 These targets were lysed by CD8+ T lymphocytes in an HLA class I-restricted manner.
176 7528768 Major histocompatibility (MHC) class I glycoproteins are specialized to present to CD8+ T cells, peptides that originate from proteins synthesized within the cytoplasm.
177 7530749 We have analyzed one such peptide, P18 from the V3 loop of HIV-1 gp160, which we have previously shown to be recognized by CD8+ CTL with the class I molecule H-2Dd, and by CD4+ Th cells with the class II molecule I-Ad.
178 7530749 Thus, the recognition of this versatile peptide by CD4+ Th cells with class II MHC molecules and by CD8+ cytotoxic T cells with class I MHC molecules is remarkably similar in both the core peptide used and the role of different residues in the ternary complex.
179 7533857 To increase the inherently weak immunogenicity of synthetic peptide vaccines, we used recombinant DNA techniques to generate chimeras between immunogenic determinants of human immunodeficiency virus type 1 (HIV-1) gp120 and antibody Fab fragments reactive with surface structures displayed specifically on human antigen-presenting cells (APCs), including surface immunoglobulin D (sIgD) and class II major histocompatibility complex (MHC) molecules.
180 7533857 Furthermore, such recombinant immunotargeted HIV-1 peptide antigens demonstrated improved immunogenicity over equivalent nonimmunotargeted control antigens, as shown by their ability to stimulate interleukin-2 production by CD4+ T-helper cells from human donors exposed to HIV-1 antigens.
181 7533857 These data suggest that immunotargeting of recombinant peptide antigens via the attached Fab fragments facilitates uptake by human APCs with subsequent access to the MHC class II processing pathway, thereby validating the immunotargeting concept for such recombinant subunit vaccines in an in vitro human system.
182 7533857 To increase the inherently weak immunogenicity of synthetic peptide vaccines, we used recombinant DNA techniques to generate chimeras between immunogenic determinants of human immunodeficiency virus type 1 (HIV-1) gp120 and antibody Fab fragments reactive with surface structures displayed specifically on human antigen-presenting cells (APCs), including surface immunoglobulin D (sIgD) and class II major histocompatibility complex (MHC) molecules.
183 7533857 Furthermore, such recombinant immunotargeted HIV-1 peptide antigens demonstrated improved immunogenicity over equivalent nonimmunotargeted control antigens, as shown by their ability to stimulate interleukin-2 production by CD4+ T-helper cells from human donors exposed to HIV-1 antigens.
184 7533857 These data suggest that immunotargeting of recombinant peptide antigens via the attached Fab fragments facilitates uptake by human APCs with subsequent access to the MHC class II processing pathway, thereby validating the immunotargeting concept for such recombinant subunit vaccines in an in vitro human system.
185 7535058 Alternative processing pathways for MHC class I-restricted epitope presentation to CD8+ cytotoxic T lymphocytes.
186 7535058 Immunization with soluble protein antigens usually primers CD4+ T cells but not CD8+ T cells because of the stringent requirements for 'endogenous processing' for major histocompatibility complex (MHC) class I-restricted epitope presentation to CD8+ CTL.
187 7535058 We describe subcellular sites, alternative peptide transport mechanisms, and alternative modes of MHC class I molecule recycling that allow different modes of peptide loading of class I molecules.
188 7535058 Alternative processing pathways for MHC class I-restricted epitope presentation to CD8+ cytotoxic T lymphocytes.
189 7535058 Immunization with soluble protein antigens usually primers CD4+ T cells but not CD8+ T cells because of the stringent requirements for 'endogenous processing' for major histocompatibility complex (MHC) class I-restricted epitope presentation to CD8+ CTL.
190 7535058 We describe subcellular sites, alternative peptide transport mechanisms, and alternative modes of MHC class I molecule recycling that allow different modes of peptide loading of class I molecules.
191 7535058 Alternative processing pathways for MHC class I-restricted epitope presentation to CD8+ cytotoxic T lymphocytes.
192 7535058 Immunization with soluble protein antigens usually primers CD4+ T cells but not CD8+ T cells because of the stringent requirements for 'endogenous processing' for major histocompatibility complex (MHC) class I-restricted epitope presentation to CD8+ CTL.
193 7535058 We describe subcellular sites, alternative peptide transport mechanisms, and alternative modes of MHC class I molecule recycling that allow different modes of peptide loading of class I molecules.
194 7537251 To identify within this 23-amino-acid peptide a shorter peptide that binds to an H-2k class I major histocompatibility molecule, a primarily CD8+ (97.8%) T-cell line (PfCSP TCL.1) was produced by immunizing B10.BR mice with recombinant vaccinia virus expressing the PfCSP and stimulating in vitro spleen cells from these immunized mice with L cells transfected with the PfCSP gene (LPF cells).
195 7541891 Autologous melanoma and peptide-pulsed BCL targets were lysed by CD8+CTL in a HLA class I-restricted manner.
196 7561107 Depletion of CD8+ T cells eliminated or markedly reduced the CTL activity, while depletion of CD4+ T cells did not affect CTL responses.
197 7561107 CTL activity was blocked by mAbs to human class I MHC Ags, but not by mAbs to class II MHC Ags.
198 7576033 Our previous reports established that immunization of mice in the footpad with a 15-amino acid synthetic peptide (R15K) from the V3 loop region in the envelope protein gp120 of human immunodeficiency virus type 1 (HIV-1) resulted in rapid induction of major histocompatability complex (MHC) class I-restricted, CD8+ HIV-1 envelope-specific cytotoxic T lymphocytes (CTLs) in the proximal popliteal lymph node.
199 7583918 Coincident with the inability to stimulate MHC-matched T cells, there was diminished surface expression of class II MHC antigens and LFA-1-alpha and LFA-3 compared with that in uninfected cells: DR, 2.5 versus 10.6% (mean channel 0.3 versus 1.5); DQ, 1.6 versus 15.6% (mean channel 0.3 versus 3.0); DP, 5.0 versus 30.9% (mean channel 0.3 versus 2.0).
200 7583918 LFA-1-alpha expression was reduced (13.1 versus 20.0%; mean channel 1.5 versus 2.0) while LFA-3 expression remained the same (22.2 versus 324%; mean channel 3.0 versus 3.3).
201 7583918 Cytokine secretion was also perturbed, as interleukin 1-alpha (IL-1-alpha) and IL-1-beta production was lost 1 week after infection.
202 7583918 Production of IL-12 and IL-10 was unchanged, while IL-6 production was increased.
203 7593618 In this report we identify HCV-specific CTL responses restricted by the HLA class I molecules A2, A3, A11, A23, B7, B8, and B53.
204 7593618 These HCV-specific CTL were shown to produce cytokines including IFN-gamma, TNF-alpha, GM-CSF, IL-8, and IL-10 in an antigen- and HLA class I-specific manner.
205 7593618 In this report we identify HCV-specific CTL responses restricted by the HLA class I molecules A2, A3, A11, A23, B7, B8, and B53.
206 7593618 These HCV-specific CTL were shown to produce cytokines including IFN-gamma, TNF-alpha, GM-CSF, IL-8, and IL-10 in an antigen- and HLA class I-specific manner.
207 7594484 In addition to the Ag-specific production of IL-2 by CD4+ peritoneal cells that was elicited, several other correlates of protective responses were noted, including dramatic induction of CD3+ and alpha beta TCR+ cell populations in the peritoneal cavity and increased expression of class II MHC and production of IL-12 (upon in vitro restimulation) by peritoneal macrophages.
208 7598771 The safety and the immunogenicity of a recombinant canarypox live vector expressing the human immunodeficiency virus type 1 (HIV-1) gp160 gene from the MN isolate, ALVAC-HIV (vCP125), followed by booster injections of a soluble recombinant hybrid envelope glycoprotein MN/LAI (rgp160), were evaluated in vaccinia-immune, healthy adults at low risk for acquiring HIV-1 infection.
209 7598771 An envelope-specific cytotoxic lymphocyte activity was found in 39% of the volunteers and characterized for some of them as CD3+, CD8+, MHC class I restricted.
210 7614984 Uptake of microparticle-adsorbed protein antigen by bone marrow-derived dendritic cells results in up-regulation of interleukin-1 alpha and interleukin-12 p40/p35 and triggers prolonged, efficient antigen presentation.
211 7614984 This is evidenced by the de novo synthesis of transcripts of interleukin-1 alpha and interleukin-12 p40/p35 as well as transcripts of MHC class II.
212 7650399 We now describe a chimeric peptide that induces Abs to native ZP3 regardless of the MHC haplotype of the inbred mice tested.
213 7650399 The design of the vaccine chimeric peptide is governed by the inclusion of two essential components: 1) a promiscuous foreign T cell peptide capable of eliciting a Th cell response regardless of the MHC haplotype of the animals, and 2) the native B cell peptide of ZP3 that has been modified by substitution of residue(s) critical for T cell but not B cell response to ZP3.
214 7650399 We now describe a chimeric peptide that induces Abs to native ZP3 regardless of the MHC haplotype of the inbred mice tested.
215 7650399 The design of the vaccine chimeric peptide is governed by the inclusion of two essential components: 1) a promiscuous foreign T cell peptide capable of eliciting a Th cell response regardless of the MHC haplotype of the animals, and 2) the native B cell peptide of ZP3 that has been modified by substitution of residue(s) critical for T cell but not B cell response to ZP3.
216 7679744 Complement depletion and monoclonal antibody inhibition studies suggest that the effector population is the major histocompatibility complex (MHC) class II-restricted CD4+ T-helper cell.
217 7685660 CD2 binds specifically to the surface glycoprotein LFA-3.
218 7685660 CD2/LFA-3 adhesion is the basis for the formation of rosettes between T cells and sheep erythrocytes (SRBC) which bear the sheep homologue of LFA-3.
219 7685660 More importantly, CD2/LFA-3 adhesion functions in the immune system to augment T cell activation; it initiates conjugate formation between participating T cells and antigen-presenting cells (APC).
220 7685660 We investigated the effects of soluble forms of CD2 (sCD2), produced in either baculovirus or CHO expression systems, on the rosetting of T cells with SRBC and on the activation of T cells by antigen plus major histocompatibility complex (MHC) molecules.
221 7685660 These findings are consistent with the notion that the CD2/LFA-3 interaction augments antigen-specific T cell functions.
222 7685660 The use of a CD2 "decoy" molecule rather than anti-CD2 or anti-LFA-3 antibodies to block the CD2/LFA-3 interaction rules out secondary antibody effects, via the Fc portion, as the basis for inhibition of T cell activation and directly stresses the importance of this adhesion interaction in T cell responses.
223 7690412 The role of major histocompatibility complex (MHC) class I-restricted CD8+ cytotoxic T lymphocytes in immunity to rubella virus (RV) infection is unknown.
224 7690412 Lymphocytes of RV-immune individuals were prestimulated on an RV-infected MHC class I-matched (or partially matched) fibroblast monolayer which generated CD8+ lymphoblasts capable of lysing RV-infected fibroblast targets in a class I-restricted manner.
225 7690412 The role of major histocompatibility complex (MHC) class I-restricted CD8+ cytotoxic T lymphocytes in immunity to rubella virus (RV) infection is unknown.
226 7690412 Lymphocytes of RV-immune individuals were prestimulated on an RV-infected MHC class I-matched (or partially matched) fibroblast monolayer which generated CD8+ lymphoblasts capable of lysing RV-infected fibroblast targets in a class I-restricted manner.
227 7691965 Traditional subunit vaccines have not elicited virus-specific CD8+ MHC class I-restricted CTL.
228 7691965 We found that both the CTL epitope peptide-helper peptide conjugate and the CTL epitope peptide alone, when delivered in an emulsion with IFA, induced CTL epitope-specific CD8+ MHC class I-restricted CTL.
229 7691965 Traditional subunit vaccines have not elicited virus-specific CD8+ MHC class I-restricted CTL.
230 7691965 We found that both the CTL epitope peptide-helper peptide conjugate and the CTL epitope peptide alone, when delivered in an emulsion with IFA, induced CTL epitope-specific CD8+ MHC class I-restricted CTL.
231 7692684 Recently, by sequencing the whole set of self-peptides eluted from a given MHC class I molecule, Falk and colleagues have found that they have a homogeneous 8-10 residue length and contain allele-specific peptidic motifs with two conservative dominant anchor residues.
232 7705811 T-cell responses to the components of pyruvate dehydrogenase complex in primary biliary cirrhosis.
233 7705811 Primary biliary cirrhosis (PBC) is an autoimmune condition that results in destruction of the intrahepatic biliary epithelial cells and is characterized by autoantibodies to pyruvate dehydrogenase complex (PDC).
234 7705811 The portal tract T-cell infiltrate and up-regulation of HLA class I, HLA class II, and cell adhesion molecules such as intercellular adhesion molecule-1 on the biliary epithelial cells suggest that T cells play a significant role in mediating this damage.
235 7707540 To identify the potential antigens involved in this protection, macaques were immunized with uninfected human cells, sucrose density gradient-purified culture fluid from uninfected human cells (mock virus), beta-2 microglobulin (beta 2M), immunoaffinity-purified HLA class I and class II proteins from these human cells, and adjuvant.
236 7732659 An analysis of the role of skin Langerhans cells (LC) in the cytoplasmic processing of HIV-1 peptides after "peplotion" transepidermal transfer and HLA class I presentation to CD8+ CTLs--an approach to immunization of humans.
237 7732659 This molecular activity was reviewed to combine the knowledge of peptide presentation by MHC and HLA class I and class II molecules to prime CD8+ cytotoxic T cells (CTLs) and CD4+ T helper cells, respectively.
238 7732659 An analysis of the role of skin Langerhans cells (LC) in the cytoplasmic processing of HIV-1 peptides after "peplotion" transepidermal transfer and HLA class I presentation to CD8+ CTLs--an approach to immunization of humans.
239 7732659 This molecular activity was reviewed to combine the knowledge of peptide presentation by MHC and HLA class I and class II molecules to prime CD8+ cytotoxic T cells (CTLs) and CD4+ T helper cells, respectively.
240 7734422 Mutations in residue 61 of H-Ras p21 protein influence MHC class II presentation.
241 7734422 The H-Ras p21 protein with the 61L mutation (61L) was processed by syngeneic splenocytes and the epitope dependent on 61L was recognized as efficiently as the corresponding peptide by the T cell hybridoma specific for 61L.
242 7742526 The ability of a series of synthetic peptides corresponding to the junctional sequences of chronic myelogenous leukemia (CML)-derived bcr-abl and acute promyelocytic leukemia (APL)-derived PML-RAR alpha fusion proteins to bind to purified class I molecules was studied.
243 7742526 Twenty-one CML peptides and 4 APL peptides were predicted to be potential HLA class I binders.
244 7742526 None of the CML b2a2 or PML-RAR alpha A or B junctional peptides showed affinity of this magnitude for the HLA class I molecules tested.
245 7742526 The ability of a series of synthetic peptides corresponding to the junctional sequences of chronic myelogenous leukemia (CML)-derived bcr-abl and acute promyelocytic leukemia (APL)-derived PML-RAR alpha fusion proteins to bind to purified class I molecules was studied.
246 7742526 Twenty-one CML peptides and 4 APL peptides were predicted to be potential HLA class I binders.
247 7742526 None of the CML b2a2 or PML-RAR alpha A or B junctional peptides showed affinity of this magnitude for the HLA class I molecules tested.
248 7755513 We have also shown that synthetic peptides representing sequences from the amino-acid repeat regions of Pf155/RESA stimulate T-cells from P. falciparum primed donors to proliferate, to release IFN-gamma and/or IL-4.
249 7755513 CD4+ T-cells recognize the antigen in the context of MHC class II molecules.
250 7768622 Mice with a homologous deletion of the beta 2-microglobulin gene (beta 2m-) are deficient in class I major histocompatibility complex molecules (MHC) and consequently are deficient in CD8+ T cells.
251 7768622 These data document the kinetics of gamma delta T cells reactive to mycobacterial antigens in vivo without class I MHC restriction and support a role for class I MHC and CD8+ T cells in the in vivo regulation of gamma delta T cells.
252 7768622 Mice with a homologous deletion of the beta 2-microglobulin gene (beta 2m-) are deficient in class I major histocompatibility complex molecules (MHC) and consequently are deficient in CD8+ T cells.
253 7768622 These data document the kinetics of gamma delta T cells reactive to mycobacterial antigens in vivo without class I MHC restriction and support a role for class I MHC and CD8+ T cells in the in vivo regulation of gamma delta T cells.
254 7790029 In this study, permissive recognition of p61-80 was analysed in three murine MHC haplotypes (H-2b,d and k) with respect to: (i) T-cell-epitope core structure; (ii) I-A/I-E class II MHC restriction; and (iii) the identification of critical amino acid residues within the core region.
255 7796673 Many tumours express tumour-specific antigens capable of being presented to CD8+ T cells by major histocompatibility complex (MHC) class I molecules.
256 7823968 Identification of potential CTL epitopes of tumor-associated antigen MAGE-1 for five common HLA-A alleles.
257 7823968 All possible peptides of nine and ten residues, containing binding motifs for HLA-A1, -A2.1, A-3.2, -A11 and -A24 were synthesized and tested for binding using a quantitative assay.
258 7871759 Dengue fever virus and Japanese encephalitis virus synthetic peptides, with motifs to fit HLA class I haplotypes prevalent in human populations in endemic regions, can be used for application to skin Langerhans cells to prime antiviral CD8+ cytotoxic T cells (CTLs)--a novel approach to the protection of humans.
259 7871759 Flaviviruses were reported to induce CD8+ cytotoxic T cells in infected individuals, indicating that nonapeptides, proteolytic cleavage products of the viral precursor protein, enter the endoplasmic reticulum in infected cells and interact with HLA class I molecules.
260 7871759 The assembled HLA class I molecules are transported to the plasma membrane and prime CD8+ T cells.
261 7871759 Dengue fever virus and Japanese encephalitis virus synthetic peptides, with motifs to fit HLA class I haplotypes prevalent in human populations in endemic regions, can be used for application to skin Langerhans cells to prime antiviral CD8+ cytotoxic T cells (CTLs)--a novel approach to the protection of humans.
262 7871759 Flaviviruses were reported to induce CD8+ cytotoxic T cells in infected individuals, indicating that nonapeptides, proteolytic cleavage products of the viral precursor protein, enter the endoplasmic reticulum in infected cells and interact with HLA class I molecules.
263 7871759 The assembled HLA class I molecules are transported to the plasma membrane and prime CD8+ T cells.
264 7871759 Dengue fever virus and Japanese encephalitis virus synthetic peptides, with motifs to fit HLA class I haplotypes prevalent in human populations in endemic regions, can be used for application to skin Langerhans cells to prime antiviral CD8+ cytotoxic T cells (CTLs)--a novel approach to the protection of humans.
265 7871759 Flaviviruses were reported to induce CD8+ cytotoxic T cells in infected individuals, indicating that nonapeptides, proteolytic cleavage products of the viral precursor protein, enter the endoplasmic reticulum in infected cells and interact with HLA class I molecules.
266 7871759 The assembled HLA class I molecules are transported to the plasma membrane and prime CD8+ T cells.
267 7896956 Antigens arising outside the cell (e.g., bacteria) are phagocytosed and processed by the exogenous pathway for presentation on MHC class II molecules (e.g., DR) to CD4+ cells.
268 7896956 Antigens derived from the cytoplasm (e.g., viral proteins) are processed by the endogenous pathway for presentation by MHC class I molecules (e.g., HLA-A, -B, -C) to CD8+ cells.
269 7896956 Antigens arising outside the cell (e.g., bacteria) are phagocytosed and processed by the exogenous pathway for presentation on MHC class II molecules (e.g., DR) to CD4+ cells.
270 7896956 Antigens derived from the cytoplasm (e.g., viral proteins) are processed by the endogenous pathway for presentation by MHC class I molecules (e.g., HLA-A, -B, -C) to CD8+ cells.
271 7897222 Using a receptor-mediated, adenovirus-augmented gene delivery system (transferrinfection) we have shown that, upon transfection with an IL-2 gene construct, MHC class I+/class II- murine M-3 cells lose their tumorigenicity in both athymic and euthymic mice.
272 7897222 Transfer of either CD4+ or CD8+ T cells led to only partial protection against challenge with wild-type M-3 cells.
273 7897222 Our further observations that T cell-enriched, but not T cell-depleted splenocytes of immunized animals are capable of tumor-specific lytic activity and that this activity resides in the CD8+ cell population are compatible with the assumption that MHC class I-restricted T cell cytotoxicity is a biologically relevant effector mechanism in this model.
274 7897222 Using a receptor-mediated, adenovirus-augmented gene delivery system (transferrinfection) we have shown that, upon transfection with an IL-2 gene construct, MHC class I+/class II- murine M-3 cells lose their tumorigenicity in both athymic and euthymic mice.
275 7897222 Transfer of either CD4+ or CD8+ T cells led to only partial protection against challenge with wild-type M-3 cells.
276 7897222 Our further observations that T cell-enriched, but not T cell-depleted splenocytes of immunized animals are capable of tumor-specific lytic activity and that this activity resides in the CD8+ cell population are compatible with the assumption that MHC class I-restricted T cell cytotoxicity is a biologically relevant effector mechanism in this model.
277 7901150 This is recognized by immune CD4 T cells which function as essential helper cells in the generation of the CD8 CTL response.
278 7901150 The existence of two types of cognate T cell responses in a syngeneic anti-tumour response was directly proved by the establishment of two types of tumour specific T cell lines which required as co-stimulator either MHC class II positive APC or IL-2.
279 7901150 The generation of the tumour specific CTL response could be blocked by monoclonal antibodies against all the molecules involved in the cognate interactions (i.e. class I MHC, CD8, class II MHC, CD4 and TCR) but not by anti-CD2 or anti-IgG.
280 7901150 The strict requirement for helper cells and APC could be bypassed by the addition of recombinant IL-2 but optimal triggering of CD8 CTL-precursor required viable tumour stimulator cells.
281 7901150 This well characterized in vitro assay may be useful (i) for monitoring the immune status of CD4 and CD8 immune T cells separately, for instance of tumour bearing and/or treated animals and (ii) for the development and testing of potent tumour cell vaccines with T cell stimulatory and/or co-stimulatory activities.
282 7901150 This is recognized by immune CD4 T cells which function as essential helper cells in the generation of the CD8 CTL response.
283 7901150 The existence of two types of cognate T cell responses in a syngeneic anti-tumour response was directly proved by the establishment of two types of tumour specific T cell lines which required as co-stimulator either MHC class II positive APC or IL-2.
284 7901150 The generation of the tumour specific CTL response could be blocked by monoclonal antibodies against all the molecules involved in the cognate interactions (i.e. class I MHC, CD8, class II MHC, CD4 and TCR) but not by anti-CD2 or anti-IgG.
285 7901150 The strict requirement for helper cells and APC could be bypassed by the addition of recombinant IL-2 but optimal triggering of CD8 CTL-precursor required viable tumour stimulator cells.
286 7901150 This well characterized in vitro assay may be useful (i) for monitoring the immune status of CD4 and CD8 immune T cells separately, for instance of tumour bearing and/or treated animals and (ii) for the development and testing of potent tumour cell vaccines with T cell stimulatory and/or co-stimulatory activities.
287 7908321 Mice were capable of rejecting a MHC class I- tumor challenge after immunization with an irradiated granulocyte/macrophage colony-stimulating factor (GM-CSF) transduced MHC class I- tumor vaccine.
288 7908321 This response was critically dependent on CD4+ T cells and natural killer (NK) cells, but minimally on CD8+ T cells.
289 7908321 A strong protective response against MHC class I+ variants of the tumor could be elicited when mice were immunized with irradiated MHC class I+ GM-CSF-secreting tumor cells.
290 7908321 This response required CD4+ and CD8+ T cells, and in addition, elimination of NK cells resulted in outgrowth of tumors that had lost expression of at least one MHC class I gene.
291 7908321 Mice were capable of rejecting a MHC class I- tumor challenge after immunization with an irradiated granulocyte/macrophage colony-stimulating factor (GM-CSF) transduced MHC class I- tumor vaccine.
292 7908321 This response was critically dependent on CD4+ T cells and natural killer (NK) cells, but minimally on CD8+ T cells.
293 7908321 A strong protective response against MHC class I+ variants of the tumor could be elicited when mice were immunized with irradiated MHC class I+ GM-CSF-secreting tumor cells.
294 7908321 This response required CD4+ and CD8+ T cells, and in addition, elimination of NK cells resulted in outgrowth of tumors that had lost expression of at least one MHC class I gene.
295 7908321 Mice were capable of rejecting a MHC class I- tumor challenge after immunization with an irradiated granulocyte/macrophage colony-stimulating factor (GM-CSF) transduced MHC class I- tumor vaccine.
296 7908321 This response was critically dependent on CD4+ T cells and natural killer (NK) cells, but minimally on CD8+ T cells.
297 7908321 A strong protective response against MHC class I+ variants of the tumor could be elicited when mice were immunized with irradiated MHC class I+ GM-CSF-secreting tumor cells.
298 7908321 This response required CD4+ and CD8+ T cells, and in addition, elimination of NK cells resulted in outgrowth of tumors that had lost expression of at least one MHC class I gene.
299 7908700 Volunteers immunized with this regimen have exhibited augmented humoral responses and have also developed CD4+ and CD8+ CTL specific for gp160.
300 7908700 In this report, we have identified the epitopes recognized by CD4+ and CD8+ CTL obtained from two vaccines.
301 7908700 In addition, other HLA class I-restricted CTL epitopes were identified in relatively conserved regions of gp120 and gp41, and CD4+ CTL were shown to recognize two different regions of gp120.
302 7908700 Thus, in these two volunteers, immunization with a single strain of HIV-1 induced CD4+ and CD8+ CTL that are specific for multiple conserved regions of HIV-1 and would be expected to recognize a broad range of viral isolates.
303 7927499 Here, we show by three different examples that cultured synovial fibroblasts with interferon-gamma (IFN-gamma)-induced MHC class II expression are capable of processing soluble protein for presentation to CD4+ T cells.
304 7927499 As more direct evidence for MHC class II-restricted antigen presentation, the response of a Mycobacterium tuberculosis-specific CD4+ T-cell clone isolated from rheumatoid synovial fluid was demonstrated in the presence of synovial fibroblasts.
305 7927499 Here, we show by three different examples that cultured synovial fibroblasts with interferon-gamma (IFN-gamma)-induced MHC class II expression are capable of processing soluble protein for presentation to CD4+ T cells.
306 7927499 As more direct evidence for MHC class II-restricted antigen presentation, the response of a Mycobacterium tuberculosis-specific CD4+ T-cell clone isolated from rheumatoid synovial fluid was demonstrated in the presence of synovial fibroblasts.
307 7975267 The available knowledge of the amino acid motifs in MHC and HLA class I-bound viral peptides priming the CD8+ cytotoxic T cell responses must be coupled with the understanding of the three-dimensional structure of BoLA class I.
308 7975271 Antiviral CD8+ CTLs are induced by viral peptides presented within the peptide binding grooves of HLA class I molecules present on the surface of infected cells.
309 7975271 Studies in the last decade provided an insight into the presentation of viral peptides by HLA class I molecules to CD8+ T cells.
310 7975271 Antiviral CD8+ CTLs are induced by viral peptides presented within the peptide binding grooves of HLA class I molecules present on the surface of infected cells.
311 7975271 Studies in the last decade provided an insight into the presentation of viral peptides by HLA class I molecules to CD8+ T cells.
312 7981310 The cytotoxic activity was mediated by CD8+, major histocompatibility complex (MHC)-restricted CTL.
313 7994925 Both CD4+ and CD8+ subpopulations responded as determined by panning experiments and by testing of phenotypically homogeneous cultures obtained by limiting dilution.
314 7994925 Studies of a stable CD8+ subline of the expanded T cells indicated that the response to DNP-modified cells was MHC-restricted, since it was blocked by antibody to class I determinants.
315 7994925 Finally, the CD8+ subline killed DNP-modified autologous melanoma cells, but not an HLA-A mismatched allogeneic melanoma, in a 6-hr 51Cr-release assay.
316 7994925 Both CD4+ and CD8+ subpopulations responded as determined by panning experiments and by testing of phenotypically homogeneous cultures obtained by limiting dilution.
317 7994925 Studies of a stable CD8+ subline of the expanded T cells indicated that the response to DNP-modified cells was MHC-restricted, since it was blocked by antibody to class I determinants.
318 7994925 Finally, the CD8+ subline killed DNP-modified autologous melanoma cells, but not an HLA-A mismatched allogeneic melanoma, in a 6-hr 51Cr-release assay.
319 7998914 In order to characterize allele-specific motifs for a larger number of alleles, the HLA-A alleles A1, A3, A11, and A24, which represent some of the most common alleles found in different ethnic populations, were chosen.
320 8002030 The HIV-1 envelope protein contains several regions with amino acid homology to HLA class I and class II molecules.
321 8002030 Independent measures of autoantibodies to Ro/SS-A and La/SS-B remained undetectable.
322 8046353 Cytotoxic T lymphocytes (CTL) specific for SIV envelope protein were detected in three of four protected animals vs. one of four unprotected animals, suggesting a possible role of MHC class I-restricted CTL in protection from infected blood cells.
323 8093457 In our study, we have analyzed the effect of amino acid substitution in a major CD4+ T cell determinant (T1) of HIV-1 gp160 on binding and recognition in the context of various E alpha E beta MHC class II molecules.
324 8093683 The modulation of MHC class II antigen and intercellular adhesion molecule-1 (ICAM-1) expression were studied.
325 8093683 Urine from the sixth instillation, however, proved to be a potent immunomodulatory agent, inducing MHC class II molecule and ICAM-1 expression.
326 8093683 The modulation of MHC class II antigen and intercellular adhesion molecule-1 (ICAM-1) expression were studied.
327 8093683 Urine from the sixth instillation, however, proved to be a potent immunomodulatory agent, inducing MHC class II molecule and ICAM-1 expression.
328 8097759 An HIV-1 envelope protein vaccine elicits a functionally complex human CD4+ T cell response that includes cytolytic T lymphocytes.
329 8097759 Antibody blocking and single cell cloning experiments demonstrated that the vaccine-induced cytolytic activity was mediated by CD4+, MHC class II-restricted T cells.
330 8097759 Longitudinal and cross-sectional studies revealed that the CD4+ CTL response was regulated in a complex manner and was not clearly correlated with MHC class II genotype, Ag dose, or number of immunizations.
331 8097759 Analysis of cytokine secretion by gp160-specific CD4+ T cell clones revealed Th0-, Th1-, and Th2-like patterns, with CD4+ CTL clones showing Th0- or T'1-like patterns.
332 8097759 Interestingly, many Th0- and Th1-like CTL clones produced very little IL-2, a finding that may explain the complicated regulation of this response.
333 8097759 An HIV-1 envelope protein vaccine elicits a functionally complex human CD4+ T cell response that includes cytolytic T lymphocytes.
334 8097759 Antibody blocking and single cell cloning experiments demonstrated that the vaccine-induced cytolytic activity was mediated by CD4+, MHC class II-restricted T cells.
335 8097759 Longitudinal and cross-sectional studies revealed that the CD4+ CTL response was regulated in a complex manner and was not clearly correlated with MHC class II genotype, Ag dose, or number of immunizations.
336 8097759 Analysis of cytokine secretion by gp160-specific CD4+ T cell clones revealed Th0-, Th1-, and Th2-like patterns, with CD4+ CTL clones showing Th0- or T'1-like patterns.
337 8097759 Interestingly, many Th0- and Th1-like CTL clones produced very little IL-2, a finding that may explain the complicated regulation of this response.
338 8179960 An immunodominant CTL epitope from the HIV-1 IIIB envelope protein gp160 comprising 15 amino acids (residues 315-329: RIQRGPGRAFVTIGK) (P18IIIB) has been identified that is recognized by class I MHC molecule H-2d-restricted murine CD8+ CTLs.
339 8223850 It has been proposed that MHC class I products also can capture peptides from "exogenous" or noninfectious sources, and this assumption underlies the use of intact proteins as vaccines for CD8+ cytotoxic T lymphocytes.
340 8228800 Emergence of NK1.1+ cells as effectors of IFN-gamma dependent immunity to Toxoplasma gondii in MHC class I-deficient mice.
341 8228800 In order to further assess the role of CD8+ cells in resistance against this protozoan we examined the ability of beta 2m-deficient mice, which fail to express MHC class I molecules and peripheral CD8+ lymphocytes, to survive tachyzoite challenge following vaccination with an attenuated parasite mutant.
342 8228800 However, high levels of IFN-gamma were secreted when the cells were cultured in vitro with soluble T. gondii lysate, and this response was abolished by NK1.1+ but not CD4+ and CD8+ lymphocyte depletion, implicating the NK1.1+ population as the major source of IFN-gamma.
343 8228800 Together, the data suggest that in class I-deficient mice vaccinated against T. gondii, the absence of CD8+ effector cells is compensated for by the emergence of a population of NK1.1+ and asialo GM1+ cells which lack cytolytic activity, and that the protective action of these cells against the parasite is attributable to IFN-gamma production.
344 8228800 Emergence of NK1.1+ cells as effectors of IFN-gamma dependent immunity to Toxoplasma gondii in MHC class I-deficient mice.
345 8228800 In order to further assess the role of CD8+ cells in resistance against this protozoan we examined the ability of beta 2m-deficient mice, which fail to express MHC class I molecules and peripheral CD8+ lymphocytes, to survive tachyzoite challenge following vaccination with an attenuated parasite mutant.
346 8228800 However, high levels of IFN-gamma were secreted when the cells were cultured in vitro with soluble T. gondii lysate, and this response was abolished by NK1.1+ but not CD4+ and CD8+ lymphocyte depletion, implicating the NK1.1+ population as the major source of IFN-gamma.
347 8228800 Together, the data suggest that in class I-deficient mice vaccinated against T. gondii, the absence of CD8+ effector cells is compensated for by the emergence of a population of NK1.1+ and asialo GM1+ cells which lack cytolytic activity, and that the protective action of these cells against the parasite is attributable to IFN-gamma production.
348 8242663 Interleukin-4 plus tumor necrosis factor alpha augments the antigenicity of melanoma cells.
349 8242663 We previously reported that interleukin 4 (IL-4) and either tumor necrosis factor alpha (TNF) or interferon gamma (IFN) synergistically inhibit melanoma cell growth and induce cell differentiation.
350 8242663 In the present study we used various combinations of IL-4, IFN and TNF to enhance the antigenicity of melanoma cells.
351 8242663 IL-4 plus TNF significantly increased the ability of melanoma cells to stimulate cytotoxic T cells (CTL) and act as targets of these CTL; IL-4 plus IFN was somewhat less effective, while TNF plus IFN was not as effective.
352 8242663 IL-4 plus TNF also increased the expression of HLA class I and HLA-DR antigens on melanoma cells.
353 8242663 These preclinical results suggest that the immune response to melanoma whole-cell vaccines might be enhanced by pretreating vaccine cells with IL-4 plus TNF.
354 8283036 Spleen cells from compound-peptide-immunized mice of three MHC haplotypes sharing the Dd class I MHC molecule but with different class II molecules exhibited enhanced gp160-specific CD8+ CTL activity and CD4+ Th.
355 8303307 It is now well established that the major histocompatibility complex (MHC)-restricted nature of T-cell recognition is due to the interaction of the T-cell antigen receptor with MHC class I or II molecules bearing short peptides derived from antigenic proteins.
356 8335968 The gp160-specific cytolysis was severely reduced or abolished by depletion of CD8+ cells and was not detected using HLA class I-mismatched target cells.
357 8368734 In addition to "classical" CD8+ Tc, CD4+ Tc were cloned from the blood of immunized patients.
358 8368734 CD4+ Tc were restricted by HLA Class I antigens, as judged by their killing of HLA Class II-negative melanomas and blocking by anti-class I antibodies.
359 8368734 Other CD4+ clones were blocked by both anti-HLA Class I or anti-Class II MHC monoclonal antibodies, and only two were blocked only by anti-HLA Class II.
360 8368734 Immunohistory revealed CD4+ and CD8+ T cells in lesions under rejection, but the predominant cells were macrophages, suggesting delayed-type hypersensitivity as a possible mechanism.
361 8368734 IFN-alpha 2 b salvaged 8 of 18 patients who failed with the theraccine, regardless of MHC phenotype, perhaps through upregulation of MHC and tumor epitopes on the autochthonous tumor.
362 8368734 In addition to "classical" CD8+ Tc, CD4+ Tc were cloned from the blood of immunized patients.
363 8368734 CD4+ Tc were restricted by HLA Class I antigens, as judged by their killing of HLA Class II-negative melanomas and blocking by anti-class I antibodies.
364 8368734 Other CD4+ clones were blocked by both anti-HLA Class I or anti-Class II MHC monoclonal antibodies, and only two were blocked only by anti-HLA Class II.
365 8368734 Immunohistory revealed CD4+ and CD8+ T cells in lesions under rejection, but the predominant cells were macrophages, suggesting delayed-type hypersensitivity as a possible mechanism.
366 8368734 IFN-alpha 2 b salvaged 8 of 18 patients who failed with the theraccine, regardless of MHC phenotype, perhaps through upregulation of MHC and tumor epitopes on the autochthonous tumor.
367 8368734 In addition to "classical" CD8+ Tc, CD4+ Tc were cloned from the blood of immunized patients.
368 8368734 CD4+ Tc were restricted by HLA Class I antigens, as judged by their killing of HLA Class II-negative melanomas and blocking by anti-class I antibodies.
369 8368734 Other CD4+ clones were blocked by both anti-HLA Class I or anti-Class II MHC monoclonal antibodies, and only two were blocked only by anti-HLA Class II.
370 8368734 Immunohistory revealed CD4+ and CD8+ T cells in lesions under rejection, but the predominant cells were macrophages, suggesting delayed-type hypersensitivity as a possible mechanism.
371 8368734 IFN-alpha 2 b salvaged 8 of 18 patients who failed with the theraccine, regardless of MHC phenotype, perhaps through upregulation of MHC and tumor epitopes on the autochthonous tumor.
372 8394161 We have shown that SIVmac-infected rhesus monkeys expressing the major histocompatibility complex (MHC) class I molecule Mamu-A*01 develop a SIVmac gag-specific CTL response which recognizes a 9 amino acid fragment of the gag protein in association with Mamu-A*01.
373 8447086 Sixteen of the resulting T-lymphocyte cell lines (from the S19 and S19+IL-2 groups) were tested through indirect immunofluorescence for expression of cell surface markers CD2, CD4, CD6, CD8, major histocompatibility complex (MHC) Class II molecules and a marker expressed on a subset of helper T-lymphocytes (Th) as well as sIgM, CD1 and a MHC Class II+ monocyte/macrophage marker.
374 8447086 However, two cell lines contained significant populations (> 80%) of CD2-, CD4-, CD6-, CD8- cells that were both responsive to exogenous rBoIL-2 and were capable of exhibiting antigen-induced LP responses.
375 8514204 Expression of the cytokines interleukin-1, interleukin-6 and tumor necrosis factor, the cell adhesion molecules ICAM-1 and LFA-3 and the class II major histocompatibility molecule HLA-DR by monocytes from the elderly and young subjects was similar.
376 8523531 To identify human CTL epitopes in the NS3 region of hepatitis C virus (HCV), we modified an approach using recombinant protein and the ability of short peptides to bind to class I major histocompatibility complex (MHC) molecules.
377 8524826 The presentation of antigenic peptides by major histocompatibility complex (MHC) class II molecules to CD4+ T cells is critical to the function of the immune system.
378 8524826 The LAMP-1 sorting signal reroutes the antigen into the MHC class II processing pathway, resulting in enhanced presentation to CD4+ cells in vitro.
379 8524826 The presentation of antigenic peptides by major histocompatibility complex (MHC) class II molecules to CD4+ T cells is critical to the function of the immune system.
380 8524826 The LAMP-1 sorting signal reroutes the antigen into the MHC class II processing pathway, resulting in enhanced presentation to CD4+ cells in vitro.
381 8546414 First, the primary events in activation of CD8+ (as well as CD4+) T lymphocytes normally require professional APC capable of furnishing co-stimulatory signals to supplement the consequences of interaction of the T-cell receptor with MHC surface molecules.
382 8548765 Presentation of antigenic peptides by MHC class II molecules to CD4+ T cells is critical to the generation of antitumor immunity.
383 8548765 In an attempt to enhance MHC class II antigen processing, we linked the sorting signals of the lysosome-associated membrane protein (LAMP-1) to the cytoplasmic/nuclear human papilloma virus (HPV-16) E7 antigen, creating a chimera (Sig/E7/LAMP-1).
384 8548765 Previously, we found that expression of this chimera in vitro and in vivo with a recombinant vaccinia vector targeted E7 to endosomal and lysosomal compartments and enhanced MHC class II presentation to CD4+ T cells compared to vaccinia expressing wild-type E7.
385 8548765 All mice vaccinated with 1 x 10(7) plaque-forming units of wild-type E7-vaccinia showed progressive tumor growth when challenged with a tumorigenic dose of TC-1 tumor cells; in contrast, 80% of mice vaccinated with the chimeric Sig/E7/LAMP1 vaccinia remained tumor free 3 months after tumor injection.
386 8548765 Furthermore, treatment with the Sig/E7/LAMP-1 vaccinia vaccine cured mice with small established TC-1 tumors, whereas the wild-type E7-vaccinia showed no effect on this established tumor burden.
387 8548765 Presentation of antigenic peptides by MHC class II molecules to CD4+ T cells is critical to the generation of antitumor immunity.
388 8548765 In an attempt to enhance MHC class II antigen processing, we linked the sorting signals of the lysosome-associated membrane protein (LAMP-1) to the cytoplasmic/nuclear human papilloma virus (HPV-16) E7 antigen, creating a chimera (Sig/E7/LAMP-1).
389 8548765 Previously, we found that expression of this chimera in vitro and in vivo with a recombinant vaccinia vector targeted E7 to endosomal and lysosomal compartments and enhanced MHC class II presentation to CD4+ T cells compared to vaccinia expressing wild-type E7.
390 8548765 All mice vaccinated with 1 x 10(7) plaque-forming units of wild-type E7-vaccinia showed progressive tumor growth when challenged with a tumorigenic dose of TC-1 tumor cells; in contrast, 80% of mice vaccinated with the chimeric Sig/E7/LAMP1 vaccinia remained tumor free 3 months after tumor injection.
391 8548765 Furthermore, treatment with the Sig/E7/LAMP-1 vaccinia vaccine cured mice with small established TC-1 tumors, whereas the wild-type E7-vaccinia showed no effect on this established tumor burden.
392 8548765 Presentation of antigenic peptides by MHC class II molecules to CD4+ T cells is critical to the generation of antitumor immunity.
393 8548765 In an attempt to enhance MHC class II antigen processing, we linked the sorting signals of the lysosome-associated membrane protein (LAMP-1) to the cytoplasmic/nuclear human papilloma virus (HPV-16) E7 antigen, creating a chimera (Sig/E7/LAMP-1).
394 8548765 Previously, we found that expression of this chimera in vitro and in vivo with a recombinant vaccinia vector targeted E7 to endosomal and lysosomal compartments and enhanced MHC class II presentation to CD4+ T cells compared to vaccinia expressing wild-type E7.
395 8548765 All mice vaccinated with 1 x 10(7) plaque-forming units of wild-type E7-vaccinia showed progressive tumor growth when challenged with a tumorigenic dose of TC-1 tumor cells; in contrast, 80% of mice vaccinated with the chimeric Sig/E7/LAMP1 vaccinia remained tumor free 3 months after tumor injection.
396 8548765 Furthermore, treatment with the Sig/E7/LAMP-1 vaccinia vaccine cured mice with small established TC-1 tumors, whereas the wild-type E7-vaccinia showed no effect on this established tumor burden.
397 8598323 Tumor cells from 7 freshly isolated human ovarian tumors and 2 continuous human ovarian cancer cell lines were analyzed for their surface expression of MHC class-1, class 11 and ICAM-1 surface antigens before and after exposure to gamma-irradiation and/or the cytokines TNF-alpha plus IFN-gamma.
398 8598323 All 7 fresh tumors expressed high levels of MHC class 1 and 1CAM-1 antigens, and levels were markedly up-regulated after exposure to TNF-alpha plus IFN-gamma Similarly, class-11 antigens were either induced (3 out of 7 tumors) or significantly up-regulated by TNF-alpha plus IFN-gamma.
399 8598323 Exposure to high doses of gamma-irradiation also increased the expression of MHC class-1 and ICAM-1 antigens, albeit to a modest degree.
400 8598323 MHC class 1 and ICAM-1 antigens expression was much lower on continuous human ovarian cell lines than on the fresh tumors.
401 8598323 Exposure of these cells to TNF-alpha plus IFN-gamma markedly up-regulated antigen expression to levels comparable to those expressed on the freshly isolated tumors.
402 8598323 Tumor cells from 7 freshly isolated human ovarian tumors and 2 continuous human ovarian cancer cell lines were analyzed for their surface expression of MHC class-1, class 11 and ICAM-1 surface antigens before and after exposure to gamma-irradiation and/or the cytokines TNF-alpha plus IFN-gamma.
403 8598323 All 7 fresh tumors expressed high levels of MHC class 1 and 1CAM-1 antigens, and levels were markedly up-regulated after exposure to TNF-alpha plus IFN-gamma Similarly, class-11 antigens were either induced (3 out of 7 tumors) or significantly up-regulated by TNF-alpha plus IFN-gamma.
404 8598323 Exposure to high doses of gamma-irradiation also increased the expression of MHC class-1 and ICAM-1 antigens, albeit to a modest degree.
405 8598323 MHC class 1 and ICAM-1 antigens expression was much lower on continuous human ovarian cell lines than on the fresh tumors.
406 8598323 Exposure of these cells to TNF-alpha plus IFN-gamma markedly up-regulated antigen expression to levels comparable to those expressed on the freshly isolated tumors.
407 8598323 Tumor cells from 7 freshly isolated human ovarian tumors and 2 continuous human ovarian cancer cell lines were analyzed for their surface expression of MHC class-1, class 11 and ICAM-1 surface antigens before and after exposure to gamma-irradiation and/or the cytokines TNF-alpha plus IFN-gamma.
408 8598323 All 7 fresh tumors expressed high levels of MHC class 1 and 1CAM-1 antigens, and levels were markedly up-regulated after exposure to TNF-alpha plus IFN-gamma Similarly, class-11 antigens were either induced (3 out of 7 tumors) or significantly up-regulated by TNF-alpha plus IFN-gamma.
409 8598323 Exposure to high doses of gamma-irradiation also increased the expression of MHC class-1 and ICAM-1 antigens, albeit to a modest degree.
410 8598323 MHC class 1 and ICAM-1 antigens expression was much lower on continuous human ovarian cell lines than on the fresh tumors.
411 8598323 Exposure of these cells to TNF-alpha plus IFN-gamma markedly up-regulated antigen expression to levels comparable to those expressed on the freshly isolated tumors.
412 8598323 Tumor cells from 7 freshly isolated human ovarian tumors and 2 continuous human ovarian cancer cell lines were analyzed for their surface expression of MHC class-1, class 11 and ICAM-1 surface antigens before and after exposure to gamma-irradiation and/or the cytokines TNF-alpha plus IFN-gamma.
413 8598323 All 7 fresh tumors expressed high levels of MHC class 1 and 1CAM-1 antigens, and levels were markedly up-regulated after exposure to TNF-alpha plus IFN-gamma Similarly, class-11 antigens were either induced (3 out of 7 tumors) or significantly up-regulated by TNF-alpha plus IFN-gamma.
414 8598323 Exposure to high doses of gamma-irradiation also increased the expression of MHC class-1 and ICAM-1 antigens, albeit to a modest degree.
415 8598323 MHC class 1 and ICAM-1 antigens expression was much lower on continuous human ovarian cell lines than on the fresh tumors.
416 8598323 Exposure of these cells to TNF-alpha plus IFN-gamma markedly up-regulated antigen expression to levels comparable to those expressed on the freshly isolated tumors.
417 8609407 Results show that the SALSA nonrepetitive sequence defines 1) major B cell epitopes, as shown by a high prevalence of Abs to each peptide in three African areas differing in their level of endemicity; 2) Th epitopes, as demonstrated by lymphoproliferation and IFN-gamma secretion in cells from the individuals from one of the low transmission areas, as well as helper effect upon Ab secretion in mice; and 3) epitopes for cytolytic lymphocytes, demonstrated in immunized and sporozoite-challenged chimpanzees, and associated with MHC class I leukocyte Ags.
418 8617963 MHC class I-dependent presentation of exoerythrocytic antigens to CD8+ T lymphocytes is required for protective immunity against Plasmodium berghei.
419 8617963 In this study, we wished to define the role of CD8+ T cells and MHC class I molecules by using the P. berghei malaria attenuated sporozoites (SPZ) protection model in beta 2-microglobulin (beta 2m) knockout (-/-) mice.
420 8617963 MHC class I-dependent presentation of exoerythrocytic antigens to CD8+ T lymphocytes is required for protective immunity against Plasmodium berghei.
421 8617963 In this study, we wished to define the role of CD8+ T cells and MHC class I molecules by using the P. berghei malaria attenuated sporozoites (SPZ) protection model in beta 2-microglobulin (beta 2m) knockout (-/-) mice.
422 8621152 Expression of HLA class I molecules and the transporter associated with antigen processing in hepatocellular carcinoma.
423 8621152 Although HLA-A antigens were detected by CMC in all cell lines tested, HLA-B and -C antigens were not detectable in six of seven HCC cell lines.
424 8621152 Furthermore, complementary DNA (cDNA) from each cell line was tested for the expression of HLA-A, -B, -C and the transporter associated with antigen processing genes (TAP1 and TAP2).
425 8621152 The selective loss of HLA-B and -C, but not -A, molecules (which also excludes a beta 2-microglobulin defect) is intriguing, and may be attributable to the ability of some of the HLA-A molecules to load signal peptides not requiring TAP transport, or to natural selection of HLA-B or -C locus-specific immune surveillance.
426 8621152 Expression of HLA class I molecules and the transporter associated with antigen processing in hepatocellular carcinoma.
427 8621152 Although HLA-A antigens were detected by CMC in all cell lines tested, HLA-B and -C antigens were not detectable in six of seven HCC cell lines.
428 8621152 Furthermore, complementary DNA (cDNA) from each cell line was tested for the expression of HLA-A, -B, -C and the transporter associated with antigen processing genes (TAP1 and TAP2).
429 8621152 The selective loss of HLA-B and -C, but not -A, molecules (which also excludes a beta 2-microglobulin defect) is intriguing, and may be attributable to the ability of some of the HLA-A molecules to load signal peptides not requiring TAP transport, or to natural selection of HLA-B or -C locus-specific immune surveillance.
430 8621152 Expression of HLA class I molecules and the transporter associated with antigen processing in hepatocellular carcinoma.
431 8621152 Although HLA-A antigens were detected by CMC in all cell lines tested, HLA-B and -C antigens were not detectable in six of seven HCC cell lines.
432 8621152 Furthermore, complementary DNA (cDNA) from each cell line was tested for the expression of HLA-A, -B, -C and the transporter associated with antigen processing genes (TAP1 and TAP2).
433 8621152 The selective loss of HLA-B and -C, but not -A, molecules (which also excludes a beta 2-microglobulin defect) is intriguing, and may be attributable to the ability of some of the HLA-A molecules to load signal peptides not requiring TAP transport, or to natural selection of HLA-B or -C locus-specific immune surveillance.
434 8621152 Expression of HLA class I molecules and the transporter associated with antigen processing in hepatocellular carcinoma.
435 8621152 Although HLA-A antigens were detected by CMC in all cell lines tested, HLA-B and -C antigens were not detectable in six of seven HCC cell lines.
436 8621152 Furthermore, complementary DNA (cDNA) from each cell line was tested for the expression of HLA-A, -B, -C and the transporter associated with antigen processing genes (TAP1 and TAP2).
437 8621152 The selective loss of HLA-B and -C, but not -A, molecules (which also excludes a beta 2-microglobulin defect) is intriguing, and may be attributable to the ability of some of the HLA-A molecules to load signal peptides not requiring TAP transport, or to natural selection of HLA-B or -C locus-specific immune surveillance.
438 8640065 Such antigens include MAGE-1, MAGE-3, MART-1/Melan-A, gp100, tyrosinase, the tyrosinase-related antigen gp75, the antigen gp15 and the mutated CDK4 and beta-catenin gene-products.
439 8640065 This should include examination of melanoma antigen and MHC class I allele expression in the individual patient's tumour, assessment of the status of the peptide transporter molecules TAP1/TAP2 and evaluation of T-cell mediated immune responses reactive against peptides and autologous melanoma.
440 8642561 Taken together, these results and recent binding data obtained in the context of murine MHC class I molecule H-2Kd suggest that the incorporation of peptide bond surrogates in MHC class I-restricted epitopes is a useful approach to design molecules having both increased stability and high MHC-binding capacity.
441 8647175 Better knowledge of major histocompatibility complex (MHC)-peptide-T cell receptor (TcR) interactions in the CD4+ T cell response should result in a better design of immunizing peptides and is a prerequisite for the development of vaccines or anti-cytomegalovirus therapy.
442 8647175 CI --> AA substitution induced strong potentiation of HLA-DR8 binding, proliferation and interferon-gamma and interleukin-4 production, possibly due to the removal of negative effects of Cys, Ile, or both side chains.
443 8671639 A stepwise multiple regression analysis demonstrated the alleles at the HLA-class I (HLA-A and B) and class II (HLA-DRB1, DQA1, DQB1, DPA1 and DPB1) loci significantly contributed to antibody production to HBsAg.
444 8671639 The multiple correlation coefficient of antibody production to HBsAg with the HLA-DRB1 locus was highest (0.34) among all of the HLA loci, whereas those with whole HLA class I or class II loci were 0.36 or 0.44 respectively.
445 8671639 A stepwise multiple regression analysis demonstrated the alleles at the HLA-class I (HLA-A and B) and class II (HLA-DRB1, DQA1, DQB1, DPA1 and DPB1) loci significantly contributed to antibody production to HBsAg.
446 8671639 The multiple correlation coefficient of antibody production to HBsAg with the HLA-DRB1 locus was highest (0.34) among all of the HLA loci, whereas those with whole HLA class I or class II loci were 0.36 or 0.44 respectively.
447 8699005 Recombinant derived H-2Kb and beta 2-microglobulin (beta 2m) were properly folded into an MHC class I complex using the vesicular stomatitis virus (VSV)-8mer from the natural nucleocapsid proteinN52-59 (RGYVYQGL), an immunodominant Kb epitope in C57BL/6 (B6) mice.
448 8701587 Immunization with a soluble recombinant HIV protein entrapped in biodegradable microparticles induces HIV-specific CD8+ cytotoxic T lymphocytes and CD4+ Th1 cells.
449 8701587 In this study it was demonstrated that immunization with a recombinant HIV envelop (env) protein entrapped in biodegradable poly(lactide-co-glycolide) (PLG) microparticles induced consistent HIV-specific CD4+ and CD8+ T-cell responses in mice.
450 8701587 Major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocytes (CTL) responses were detected following a single systemic immunization with gp120 entrapped microparticles and when given by the intranasal (i.n.) route induced HIV-specific CD8+ CTL and secretory IgA.
451 8701587 Furthermore immunization with gp120 entrapped in microparticles generated CD4+ T cells that secreted moderate to high levels of IFN-gamma.
452 8717384 While this process can lead to the development of neutralizing antibody responses recognizing authentic protein conformations, in vivo antigen production also results in epitope presentation via the MHC class I antigen processing pathway, leading to the elicitation of cytotoxic cellular immune responses.
453 8720322 Depending on the initial extra- or intracellular localization of the microorganism, some antigenic peptides will appear on the surface of antigen presenting cells on either MHC class I or class II molecules which are specifically recognized by either CD4+ or CD8+ lymphocytes.
454 8725877 We used a retroviral vector containing a human gamma-interferon (gamma-IFN) gene to transduce 13 renal carcinoma cell lines.
455 8725877 This study confirms that retroviral vector transduction of the human gamma-IFN gene into renal carcinoma cells is feasible and associated with persistent production of gamma-IFN and increased expression of HLA class I and II molecules, and these effects are retained after irradiation and cryopreservation.
456 8729905 In this study we investigated whether B7-1 expressing neuro-2a cells can stimulate an effective T-cell response if they were cotransduced with the interferon-gamma (IFN-gamma) gene to upregulate MHC class I.
457 8732694 Effective immunization against neuroblastoma using double-transduced tumor cells secreting GM-CSF and interferon-gamma.
458 8732694 Murine neuroblastoma, neuro-2a, was transduced with the retroviral vector MFG-granulocyte-macrophage colony-stimulating factor (GM-CSF), to examine immune stimulation conferred by localized GM-CSF production.
459 8732694 Because both CD4+ and CD8+ T cells were necessary during priming to this MHC class Ilo, II-tumor, these data indicate that major histocompatibility complex (MHC) class I+, II+ antigen-presenting cells (APCs) were required for the T-cell antitumor response.
460 8732694 Co-expression of GM-CSF and IFN-gamma, both of which have immunostimulatory activities on antigen-presenting cells, abrogated the tumorigenic potential of this tumor and increased immunogenicity over N-2a/IFN but not N-2a/GM.
461 8793547 IL-2 adenovector-transduced neuroblasts are immunostimulatory; when they are cultured with patient lymphocytes, they increase the proportion of DR+ T cells and generate major histocompatibility complex (MHC) unrestricted cytotoxic effector cells active against parental (nontransduced) tumor cells.
462 8804738 It is important in the construction of adenovirus vectors not to delete a major portion of the early region 3 (E3) because: the E3 19 kD glycoprotein markedly reduces the capacity of the Class I major histocompatibility complex (Class I MHC) from transporting viral antigens to the surfaces of infected cells; and the E3 14.7 kD protein significantly inhibits the production of TNF-alpha and, therefore, reduces the polymorphonuclear response.
463 8805653 Targeted LN immunization with this vaccine elicited MHC class I-restricted CD8+ CTL responses, and the highest frequency of CTL was found in the iliac LNs.
464 8834646 [Reactivity to hepatitis B vaccination (HBV) in patients with uremia: association with defined HLA antigen configuration and complement protein allotypes C4A, C4B and B factor (Bf)].
465 8834646 Genes, which are responsible for the effectivity of immune response are located on the chromosome 6 similarly as the genes of the class I and II of the major histocompatibility complex (MHC) together with the genes of some complement proteins (C4A, C4B, B factor/Bf/).
466 8834646 The study investigates the interdependence between HLA configuration as well as complement protein allotypes (C4A, C4B, Bf) with the reactivity to HBV vaccination of ESRD [end stage renal disease]-patients. 153 ESRD-patients (68 females, 85 males; mean duration of hemodialysis therapy 8.2 +/- 5.1 years) were studied.
467 8834646 HLA typing was performed by means of microlymphocytotoxicity assay, whereas complement allotypes were estimated by using high voltage gel electrophoresis with subsequent specific immunofixation with antibodies against C4A, C4B and Bf.
468 8834646 In about 40% of NR HLA-A1, -B8, -DR3, or -DQ2 antigens occurred as homozygotes.
469 8852411 CTL activity was MHC restricted (H-2d) and was mediated by CD3+, CD8+, CD4- T-lymphocytes.
470 8871653 All Bb-specific CTL lines were CD3+, CD8+, and TCRalphabeta, and cytotoxic activity was HLA class I restricted.
471 8871653 Moreover, CD8+ T cells expanded by Ag-specific stimulation in vitro demonstrated Bb-specific and HLA class I-restricted lysis toward individual borrelial proteins.
472 8871653 All Bb-specific CTL lines were CD3+, CD8+, and TCRalphabeta, and cytotoxic activity was HLA class I restricted.
473 8871653 Moreover, CD8+ T cells expanded by Ag-specific stimulation in vitro demonstrated Bb-specific and HLA class I-restricted lysis toward individual borrelial proteins.
474 8883796 The percentage of CD4+ T cells was higher (P < 0.01), and the percentage of cells expressing major histocompatibility complex (MHC) class II antigens was lower (P < 0.001), in MDV-infected chickens than in uninfected birds.
475 8883796 In conclusion, a marked increase in the CD4+ T lymphocyte population occurred in the early stage of MDV infection in all chickens regardless of the presence of ev genes, whereas the number of cells expressing MHC class II antigen was severely reduced.
476 8883796 The percentage of CD4+ T cells was higher (P < 0.01), and the percentage of cells expressing major histocompatibility complex (MHC) class II antigens was lower (P < 0.001), in MDV-infected chickens than in uninfected birds.
477 8883796 In conclusion, a marked increase in the CD4+ T lymphocyte population occurred in the early stage of MDV infection in all chickens regardless of the presence of ev genes, whereas the number of cells expressing MHC class II antigen was severely reduced.
478 8892615 We show here that highly purified CD14(bright) peripheral blood monocytes supplemented with granulocyte-monocyte (GM)-CSF plus IL-4 develop with high efficacy (>95% of input cells) into DC.
479 8892615 They neo-expressed CD1a, CD1b, CD1c, CD80, and CD5; they massively up-regulated CD40 (109-fold) and HLA-DQ and DP (125- and 87-fold); and significantly (>5-fold) up-regulated HLA-DR, CD4, CD11b, CD11c, CD43, CD45, CD45R0, CD54, CD58, and CD59.
480 8892615 CD14, CD15s, CD64, and CDw65 molecules were down-regulated to background levels, and no major changes were observed for HLA class I, CD11a, CD32, CD33, CD48, CD50, CD86, CDw92, CD93, or CD97.
481 8892615 Monocytes cultured in parallel with GM-CSF plus TNF-alpha were more heterogeneous in expression densities but otherwise similar in their surface molecule repertoire.
482 8892615 Only GM-CSF plus IL-4-cultured cells were found to be potent stimulators in allogeneic and autologous MLR and they presented tetanus toxoid 100- to 1000-fold more efficiently than other cell populations tested.
483 8894681 Indeed, enhanced expression of HLA class I and/or ICAM-1 molecules on the surface of the TNF gene-transduced tumor cells were observed by fluorescence-activated cell sorting (FACS) analysis.
484 8906815 We have observed and analyzed an unexpected cross-reactivity of CD8+ CTL between two nonhomologous peptides of the HIV-1 IIIB gp160 envelope protein, P18 (residues 315-329) and HP53 (834-848, also called TH4.1), in the context of four different class I MHC molecules, Dd, Dp, Dq (or Lq), and H-2u.
485 8906815 Cross-reactivity was also shown in immunization in vivo and with target cells endogenously expressing viral protein in vitro using two different recombinant vaccinia viruses expressing only the N-terminal portion of gp160, containing P18 but not HP53.
486 8906815 A comparison of these peptide sequences and recent data on residues of P18 interacting with H-2Dd provided us with clues to residues involved in the interaction of the CTL with the MHC-peptide complex.
487 8906815 We have observed and analyzed an unexpected cross-reactivity of CD8+ CTL between two nonhomologous peptides of the HIV-1 IIIB gp160 envelope protein, P18 (residues 315-329) and HP53 (834-848, also called TH4.1), in the context of four different class I MHC molecules, Dd, Dp, Dq (or Lq), and H-2u.
488 8906815 Cross-reactivity was also shown in immunization in vivo and with target cells endogenously expressing viral protein in vitro using two different recombinant vaccinia viruses expressing only the N-terminal portion of gp160, containing P18 but not HP53.
489 8906815 A comparison of these peptide sequences and recent data on residues of P18 interacting with H-2Dd provided us with clues to residues involved in the interaction of the CTL with the MHC-peptide complex.
490 8920705 In this way, antigen-specific, MHC-restricted lysis by CD8+ cells was detected.
491 8947600 In the present paper, the authors show that Sm28GST is also able to stimulate an antigen-specific, cytotoxic T-cell response against Sm28GST-pulsed P815 target cells in normal mice and that effector cells induced in vivo were classical Class I MHC-restricted CD8+ lymphocytes.
492 8947600 The role of these Class I MHC-restricted CD8+ lymphocytes in the protection observed precisely at the same period in immunized mice remains to be elucidated.
493 8947600 In the present paper, the authors show that Sm28GST is also able to stimulate an antigen-specific, cytotoxic T-cell response against Sm28GST-pulsed P815 target cells in normal mice and that effector cells induced in vivo were classical Class I MHC-restricted CD8+ lymphocytes.
494 8947600 The role of these Class I MHC-restricted CD8+ lymphocytes in the protection observed precisely at the same period in immunized mice remains to be elucidated.
495 8962644 However, only mice of certain major histocompatibility complex (MHC) haplotype respond to the ZP3 peptide.
496 8962644 A chimeric peptide has been designed that induces antibody to native ZP3 regardless of the MHC haplotype of the inbred mice tested.
497 8962644 The vaccine contains (1) a promiscuous foreign T-cell peptide capable of eliciting a T-cell response regardless of the animals' MHC haplotype, and (2) a modified native B-cell peptide of ZP3.
498 8962644 However, only mice of certain major histocompatibility complex (MHC) haplotype respond to the ZP3 peptide.
499 8962644 A chimeric peptide has been designed that induces antibody to native ZP3 regardless of the MHC haplotype of the inbred mice tested.
500 8962644 The vaccine contains (1) a promiscuous foreign T-cell peptide capable of eliciting a T-cell response regardless of the animals' MHC haplotype, and (2) a modified native B-cell peptide of ZP3.
501 8962644 However, only mice of certain major histocompatibility complex (MHC) haplotype respond to the ZP3 peptide.
502 8962644 A chimeric peptide has been designed that induces antibody to native ZP3 regardless of the MHC haplotype of the inbred mice tested.
503 8962644 The vaccine contains (1) a promiscuous foreign T-cell peptide capable of eliciting a T-cell response regardless of the animals' MHC haplotype, and (2) a modified native B-cell peptide of ZP3.
504 8975917 Cowdria-specific T-cell lines generated from vaccinated animals by in vitro restimulation with Cowdria lysates are 95 to 100% CD4+, are MHC class II restricted, and produce gamma interferon.
505 8988876 MHC class I and class II gene knockout animals infected with B. abortus have demonstrated that protection to B. abortus is especially dependent on CD8+ T cells.
506 9005958 To address this issue we attempted to generate 'artificial' APC able to stimulate CD4+ T cell responses when tumor cells were infected with a single, recombinant, vaccinia virus (rVV) containing the two genes encoding murine MHC class II I-Ak and a third gene encoding the murine B7-1 (mB7-1) costimulatory molecule.
507 9009330 CD8+ T cells are essential for protection against mycobacteria, as is clearly demonstrated by the fatal outcome of experimental infection of beta-2 microglobulin knockout mice.
508 9009330 This response is mediated by CD8+ T cells and absolutely requires the activation of CD4+ T cells and their secretion of interleukin 2.
509 9009330 Our results indicate that MHC-linked genes exert a profound influence on the generation of CD8+ CTLs following BCG vaccination.
510 9012449 Transduction with the gammaIFN, but not the IL-2, gene caused significant increases in the expression of major histocompatibility complex (MHC) antigens on B16-gammaIFN cells.
511 9014294 The CTL induced were CD8+, MHC class I restricted, and could recognize virus infected cells.
512 9047023 Therefore, this study 1) provides evidence to support the feasibility of the CP strategy in hZP3 vaccine development and 2) describes a novel approach for evaluating the influence of polymorphic human MHC on vaccine immunogenicity without human immunization.
513 9052739 In BALB/c mice, intramuscular injection of either plasmid induced IgG2a antibodies associated with a Th1-like profile characterized by the in vitro splenic production of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma).
514 9052739 In control experiments, immunization using purified CAP antigen induced a predominant, but not exclusive, Th2-like profile as determined by the splenic production of IL-4 and IL-10.
515 9052739 For all CAP immunogens, MHC haplotype of immunized mice was found to influence seroconversion rates but not the type of cytokines produced in vitro.
516 9066682 Short peptides derived from MAGE-1 and MAGE-3 gene products are recognized by cytolytic T lymphocytes when presented by HLA-class-I molecules, and represent potential targets for specific immunotherapy.
517 9066682 Out of the 49 esophageal squa-mous-cell carcinomas studied, 53% expressed MAGE-1, 49% MAGE-2, 47% MAGE-3 and 71% MAGE-4.
518 9108460 We have demonstrated that B7.1-modified melanoma cells are able to induce primary CTL activity from autologous, human lymphocyte antigen (HLA) class I-matched allogeneic PBLs and purified CD8+ T cells in the absence of exogenous cytokines.
519 9108460 CTLs generated by B7.1 are tumor specific and HLA class I restricted, and CD8+ T cells are primarily responsible for this specific cytotoxicity.
520 9108460 We have demonstrated that B7.1-modified melanoma cells are able to induce primary CTL activity from autologous, human lymphocyte antigen (HLA) class I-matched allogeneic PBLs and purified CD8+ T cells in the absence of exogenous cytokines.
521 9108460 CTLs generated by B7.1 are tumor specific and HLA class I restricted, and CD8+ T cells are primarily responsible for this specific cytotoxicity.
522 9121835 We thus demonstrate that a single MAP construct, composed of peptides from distinct antigens of Schistosoma mansoni, induced a B- and T-cell response, including production of potentially protective IFN-gamma, irrespective of the MHC background.
523 9131645 The poliovirus receptor on the T-cell may require both a specific combination of V segments of the T-cell antigen receptor, as well as a specific major histocompatibility (MHC) antigen, acting in concert to infect monocytes, the primary transporter of poliovirus from blood into the brain.
524 9147700 The RCC-1 cell line constitutively expressed major histocompatibility complex (MHC) class I, intercellular adhesion molecule (ICAM)-1, and leukocyte function-associated antigen (LFA)-3 molecules, and MHC class II molecules were induced by interferon-gamma (IFN-gamma) treatment in vitro.
525 9147700 However, neither RCC-1- nor IFN-gamma-treated RCC-1 cells expressed B7-1, and both failed to induce T-cell proliferative responses in mixed lymphocyte and tumor cell reaction (MLTR) assays, suggesting that the costimulatory signals provided by cell adhesion molecules such as ICAM-1 and LFA-3 were not sufficient to elicit an antitumor immune response.
526 9155636 Intranasal antigen targeting to MHC class II molecules primes local IgA and serum IgG antibody responses in mice.
527 9155636 Our results demonstrate that immunotargeting to MHC class II molecules via the IN route allows priming of the local IgA and circulating IgG antibody, and indicate that this technique is a feasible approach for delivery of subunit vaccines in the upper respiratory tract.
528 9155636 Intranasal antigen targeting to MHC class II molecules primes local IgA and serum IgG antibody responses in mice.
529 9155636 Our results demonstrate that immunotargeting to MHC class II molecules via the IN route allows priming of the local IgA and circulating IgG antibody, and indicate that this technique is a feasible approach for delivery of subunit vaccines in the upper respiratory tract.
530 9166855 However, recent reports have shown that human PMN can express MHC class II molecules both in vitro and in vivo after stimulation with either granulocyte-macrophage colony-stimulating factor (GM-CSF) or interferon-gamma (IFN-gamma).
531 9166855 This accessory activity for SAg presentation was present only after induction of MHC class II expression, and was especially pronounced following culture of PMN with GM-CSF plus IFN-gamma, which acted synergistically to induce MHC class II molecules on PMN.
532 9166855 On the other hand, culture of PMN with GM-CSF plus IFN-gamma under conditions that resulted in optimal MHC class II expression did not enable them to function as antigen-presenting cells for either intact tetanus toxoid (TT) or for a TT peptide.
533 9166855 They also identify a donor-specific polymorphism for induction of PMN MHC class II expression which may be of significance for therapies involving GM-CSF and IFN-gamma.
534 9166855 However, recent reports have shown that human PMN can express MHC class II molecules both in vitro and in vivo after stimulation with either granulocyte-macrophage colony-stimulating factor (GM-CSF) or interferon-gamma (IFN-gamma).
535 9166855 This accessory activity for SAg presentation was present only after induction of MHC class II expression, and was especially pronounced following culture of PMN with GM-CSF plus IFN-gamma, which acted synergistically to induce MHC class II molecules on PMN.
536 9166855 On the other hand, culture of PMN with GM-CSF plus IFN-gamma under conditions that resulted in optimal MHC class II expression did not enable them to function as antigen-presenting cells for either intact tetanus toxoid (TT) or for a TT peptide.
537 9166855 They also identify a donor-specific polymorphism for induction of PMN MHC class II expression which may be of significance for therapies involving GM-CSF and IFN-gamma.
538 9166855 However, recent reports have shown that human PMN can express MHC class II molecules both in vitro and in vivo after stimulation with either granulocyte-macrophage colony-stimulating factor (GM-CSF) or interferon-gamma (IFN-gamma).
539 9166855 This accessory activity for SAg presentation was present only after induction of MHC class II expression, and was especially pronounced following culture of PMN with GM-CSF plus IFN-gamma, which acted synergistically to induce MHC class II molecules on PMN.
540 9166855 On the other hand, culture of PMN with GM-CSF plus IFN-gamma under conditions that resulted in optimal MHC class II expression did not enable them to function as antigen-presenting cells for either intact tetanus toxoid (TT) or for a TT peptide.
541 9166855 They also identify a donor-specific polymorphism for induction of PMN MHC class II expression which may be of significance for therapies involving GM-CSF and IFN-gamma.
542 9166855 However, recent reports have shown that human PMN can express MHC class II molecules both in vitro and in vivo after stimulation with either granulocyte-macrophage colony-stimulating factor (GM-CSF) or interferon-gamma (IFN-gamma).
543 9166855 This accessory activity for SAg presentation was present only after induction of MHC class II expression, and was especially pronounced following culture of PMN with GM-CSF plus IFN-gamma, which acted synergistically to induce MHC class II molecules on PMN.
544 9166855 On the other hand, culture of PMN with GM-CSF plus IFN-gamma under conditions that resulted in optimal MHC class II expression did not enable them to function as antigen-presenting cells for either intact tetanus toxoid (TT) or for a TT peptide.
545 9166855 They also identify a donor-specific polymorphism for induction of PMN MHC class II expression which may be of significance for therapies involving GM-CSF and IFN-gamma.
546 9176112 Splenocytes from MDV vaccine strain, SB-1 inoculated MHC:B19B19 and MHC:B21B21 chickens, depleted for CD4+, CD8+, TCR gamma delta +, TCR alpha beta 1+ and/or TCR alpha beta 2+ cells, were used as effector cells in chromium-release assays.
547 9192661 Interferon-gamma treatment or transduction of the class II transactivator (CIITA) gene induces class II expression but also up-regulates the class II-associated accessory molecules, invariant chain (Ii) and DM.
548 9192661 To determine if interferon-gamma treatment and CIITA transduction are potential immunotherapies, we assessed the tumorigenicity of sarcoma cells expressing combinations of class II, Ii, and DM.
549 9192661 Since we hypothesized that class II-transfected tumor cells not coexpressing Ii and DM present endogenously encoded tumor peptides, we have assessed the transfectants for antigen presentation activity to MHC class II-restricted antigen-specific CD4(+) T cells.
550 9199462 A murine model of pneumonia due to the mouse pneumonitis agent (MoPn [murine Chlamydia trachomatis]) in mice deficient in CD4+ T-cell function (major histocompatibility complex [MHC] class II function [class II-/-], CD8+ T-cell function (beta2-microglobulin deficient, MHC class I deficient [Beta2m-/-]), B-cell function (C57BL/10J-Igh(tm1Cgn) [Igh-/-]), and gamma interferon (IFN-gamma) (C57BL/6-Ifg(tm1) [Ifg-/-]) or interleukin-4 (C57BL/6J(tm1Cgn29) [IL4-/-]) production was employed to determine if each of these mechanisms was critical to resistance against reinfection by C. trachomatis or if alternate compensatory mechanisms existed in their absence which could potentially be exploited in vaccine development.
551 9199462 CD4 T-cell-deficient MHC class II-/- mice were very susceptible to reinfection with MoPn, showing the critical importance of this cell to resistance.
552 9199462 These mice lacked antibody production but did produce IFN-gamma, apparently by mechanisms involving NK and CD8+ T cells.
553 9199462 Levels of lung IFN-gamma and TNF-alpha were elevated in Igh-/- mice compared to those in controls.
554 9199462 Of most importance, however, congenitally IFN-gamma-deficient Ifg-/- mice (which have elevated levels of other cytokines, including TNF-alpha and granulocyte-macrophage colony-stimulating factor) are paradoxically more resistant to MoPn rechallenge than controls, showing that IFN-gamma is not an absolute requirement for acquired resistance and implying the presence of very effective compensatory host defense mechanism(s).
555 9199462 Thus, resistance to reinfection in this model is flexible and multifactorial and is heavily dependent on CD4+ T cells, with a probable role for IFN-gamma and TNF-alpha and a possible modest role for Th1-dependent antibody.
556 9199462 Since IFN-gamma was dispensable in host defense, the highly effective mechanism or mechanisms which can compensate for its absence (which include TNF-alpha) deserve further study.
557 9199462 A murine model of pneumonia due to the mouse pneumonitis agent (MoPn [murine Chlamydia trachomatis]) in mice deficient in CD4+ T-cell function (major histocompatibility complex [MHC] class II function [class II-/-], CD8+ T-cell function (beta2-microglobulin deficient, MHC class I deficient [Beta2m-/-]), B-cell function (C57BL/10J-Igh(tm1Cgn) [Igh-/-]), and gamma interferon (IFN-gamma) (C57BL/6-Ifg(tm1) [Ifg-/-]) or interleukin-4 (C57BL/6J(tm1Cgn29) [IL4-/-]) production was employed to determine if each of these mechanisms was critical to resistance against reinfection by C. trachomatis or if alternate compensatory mechanisms existed in their absence which could potentially be exploited in vaccine development.
558 9199462 CD4 T-cell-deficient MHC class II-/- mice were very susceptible to reinfection with MoPn, showing the critical importance of this cell to resistance.
559 9199462 These mice lacked antibody production but did produce IFN-gamma, apparently by mechanisms involving NK and CD8+ T cells.
560 9199462 Levels of lung IFN-gamma and TNF-alpha were elevated in Igh-/- mice compared to those in controls.
561 9199462 Of most importance, however, congenitally IFN-gamma-deficient Ifg-/- mice (which have elevated levels of other cytokines, including TNF-alpha and granulocyte-macrophage colony-stimulating factor) are paradoxically more resistant to MoPn rechallenge than controls, showing that IFN-gamma is not an absolute requirement for acquired resistance and implying the presence of very effective compensatory host defense mechanism(s).
562 9199462 Thus, resistance to reinfection in this model is flexible and multifactorial and is heavily dependent on CD4+ T cells, with a probable role for IFN-gamma and TNF-alpha and a possible modest role for Th1-dependent antibody.
563 9199462 Since IFN-gamma was dispensable in host defense, the highly effective mechanism or mechanisms which can compensate for its absence (which include TNF-alpha) deserve further study.
564 9218594 Interleukin-10 prevents dendritic cell accumulation and vaccination with granulocyte-macrophage colony-stimulating factor gene-modified tumor cells.
565 9218594 Because "cross-priming" of T cells by host Ag-presenting cells for MHC class I-restricted tumor Ags is a major pathway for induction of tumor immunity and that is enhanced by granulocyte-macrophage (GM) CSF, we expressed this cytokine in J558L cells.
566 9218594 Inhibition of IL-10 expression through an IL-10 antisense retrovirus restored the vaccine efficacy of GM-CSF-producing J558L cells, demonstrating a direct role of IL-10 in paralyzing the GM-CSF-induced antitumor immune response.
567 9218594 Immunohistochemical analysis of the vaccine site showed a GM-CSF-induced accumulation of dendritic cells (DC) (MHC class II+ and DEC-205+) in the absence of IL-10.
568 9218594 Together, our results demonstrate an antagonistic effect of IL-10 with respect to GM-CSF-induced DC accumulation and tumor immunity and suggest a new mechanism by which tumors escape immune recognition: namely by preventing APC from obtaining access to tumor Ags.
569 9218594 Interleukin-10 prevents dendritic cell accumulation and vaccination with granulocyte-macrophage colony-stimulating factor gene-modified tumor cells.
570 9218594 Because "cross-priming" of T cells by host Ag-presenting cells for MHC class I-restricted tumor Ags is a major pathway for induction of tumor immunity and that is enhanced by granulocyte-macrophage (GM) CSF, we expressed this cytokine in J558L cells.
571 9218594 Inhibition of IL-10 expression through an IL-10 antisense retrovirus restored the vaccine efficacy of GM-CSF-producing J558L cells, demonstrating a direct role of IL-10 in paralyzing the GM-CSF-induced antitumor immune response.
572 9218594 Immunohistochemical analysis of the vaccine site showed a GM-CSF-induced accumulation of dendritic cells (DC) (MHC class II+ and DEC-205+) in the absence of IL-10.
573 9218594 Together, our results demonstrate an antagonistic effect of IL-10 with respect to GM-CSF-induced DC accumulation and tumor immunity and suggest a new mechanism by which tumors escape immune recognition: namely by preventing APC from obtaining access to tumor Ags.
574 9220317 In 6/6 HLA A*0201-expressing melanoma patients tested, the virally driven expression of MART-1/Melan A MAA by DC was sufficient to generate CD8+ T lymphocytes that could recognize naturally processed epitopes on tumor cells.
575 9234542 The immune responses to antigen-expressing vector carrying a viral promoter such as the SV40 early promoter or the major histocompatibility (MHC) class I promoter were reduced in presence of IFN-gamma while the B and T helper cell response to a vector expressing the antigen under the control of the MHC class II promoter was not affected by this cytokine.
576 9237351 Computer simulations to identify in polyproteins of FMDV OK1 and A12 strains putative nonapeptides with amino acid motifs for binding to BoLA class I A11 and A20 haplotype molecules.
577 9237351 The computer program "Findpatterns" was used to search FMDV- (OK1 and A12 strains) coded structural and nonstructural proteins for the availability of putative proteasome-generated nonapeptides with motifs reported for BoLA class I A11 and A20 haplotypes.
578 9237351 These BoLA class I A11 and A20 nonapeptide motifs are identical to motifs of nonapeptides that interact with the peptide binding grooves of HLA class I B35 and B27 haplotypes, respectively.
579 9243749 The HLA type of these individuals and of 248 controls were determined by serology for HLA class I and by molecular typing for the HLA class II loci DRB1 and DQB1.
580 9243749 Subsequent analysis of the results revealed that HLA-DRB1*0701 and HLA-DQB1*02 were significantly associated with antibody non-response to the "S"-containing vaccine compared with the HLA control population.
581 9243749 The hepatitis B surface antigen antibody results from this group of patients show that 30 of the 86 individuals remained antibody non-responders and that 24 individuals (80%) expressed the HLA-DQB1*02 and that 21 individuals (70%) expressed HLA-DRB1*0701.
582 9247574 We have previously reported decreased tumorigenicity of the murine plasmacytoma J558L [major histocompatibility complex (MHC) class I+ and class II-] expressing IL-2 or B7.1.
583 9247574 We examined the mechanism underlying this unexpected result: 6 days after injection of J558-IL2/B7.1 cells, tumor were nearly completely destroyed and were almost devoid of CD8+ cells, while CD8+ cells were increased in both IL-2- and B7.1-transfected tumors.
584 9252123 Degenerate cytotoxic T cell epitopes from P. falciparum restricted by multiple HLA-A and HLA-B supertype alleles.
585 9252123 Positive cytotoxic T lymphocyte recall and cytokine (interferon-gamma and tumor necrosis factor alpha) responses were detected for all peptides; all were recognized in the context of more than one HLA class I molecule; and at least 12 of the 17 were recognized in the context of all HLA alleles studied.
586 9257295 While immunization can be improved, deficient MHC class I expression remains a problem, because it hampers the ability of tumor cells to present antigens for killing by CD8+ T cells.
587 9257826 When APC were exposed in vitro to such protein conjugates, they processed and presented the peptides in association with MHC class I molecules and stimulated CD8+ Ag-specific T cells.
588 9281508 Characterization of an overlapping CD8+ and CD4+ T-cell epitope on rubella capsid protein.
589 9281508 A synthetic peptide corresponding to rubella virus capsid protein residues 263 to 275 which contains an epitope recognized by a cloned CD4+ cytotoxic T-lymphocyte (CTL) line was used to induce CD8+ T-cell lines specific to this peptide.
590 9281508 Analysis of HLA class I restriction of the CD8+ CTL clone revealed that A11 and A3 were restrictive elements.
591 9281508 The identification of overlapping CD4+ and CD8+ T-cell epitopes within the capsid protein sequence C(263-275) implicates a strategy for using such epitopes in a candidate peptide-based rubella vaccine.
592 9286055 Selective activation of CD8+ and MHC-restricted SIV Gag-specific CTL was induced by stimulation with autologous para-formaldehyde-fixed B-lymphoblastoid cell lines infected with a recombinant vaccinia virus expressing SIV Gag.
593 9300034 These results illustrate that Pr55gag VLPs provide a safe and effective means of enhancing neutralizing humoral responses to particle-entrapped gp120 proteins and are also capable of delivering these proteins to the MHC class I antigen processing and presentation pathway.
594 9307066 Functionally mature Vgamma9Vdelta2 T cells display a potent natural killer (NK)-like cytotoxic activity, share with NK cells the expression of inhibitory receptors for HLA class I molecules, and release a plethora of cytokines, most notably interferon-gamma and tumor necrosis factor alpha.
595 9311595 Cytotoxic CD4+ and CD8+ T lymphocytes, generated by mutant p21-ras (12Val) peptide vaccination of a patient, recognize 12Val-dependent nested epitopes present within the vaccine peptide and kill autologous tumour cells carrying this mutation.
596 9311595 Here, we examined the capacity of CD4+ and CD8+ T cells, generated simultaneously by mutant-ras-peptide vaccination of a pancreatic-adenocarcinoma patient, to recognize and lyse autologous tumour cells harbouring corresponding activated K-ras epitopes.
597 9311595 Responding T cells were cloned following peptide stimulation, and CD4+ and CD8+ peptide-specific cytotoxic T lymphocytes(CTL) were obtained.
598 9311595 These cells were efficiently killed by the T-cell clones and CD8+-mediated cytotoxicity was HLA-class-I-restricted, as demonstrated by inhibition of lysis by anti-class-I monoclonal antibodies.
599 9311595 These data demonstrate that peptide vaccination with a single mutant p21-ras-derived peptide induces CD4+ and CD8+ CTL specific for nested epitopes, including the Gly --> Val substitution at codon 12, and that both these T-cell sub-sets specifically recognize tumour cells harbouring the corresponding K-ras mutation.
600 9322873 The melanoma cells express defined MHC Class I histocompatibility determinants including determinants specified by the HLA-A2 Class I allele, along with a common melanoma-associated T-cell epitope derived from the tyrosinase gene.
601 9334819 Identification of HLA-A*0201-restricted CTL epitopes encoded by the tumor-specific MAGE-2 gene product.
602 9334819 Moreover, CTLs against 2 of them (M2 112-120, and M2 157-166) specifically recognize cells that express both the MAGE-2 protein and HLA-A*0201Kb.
603 9334819 Identification of HLA-A*0201-restricted CTL epitopes encoded by the tumor-specific MAGE-2 gene product.
604 9334819 Moreover, CTLs against 2 of them (M2 112-120, and M2 157-166) specifically recognize cells that express both the MAGE-2 protein and HLA-A*0201Kb.
605 9334822 Notably all lines expressed HLA class I, intercellular adhesion molecule-1 (ICAM-1), polymorphic epithelial mucin (PEM) and cytokeratin (CK), but not HLA class II, B7.1 (CD80) or BAGE.
606 9334822 While of the 9 lines tested 4 (INT.Ov1, 2, 5 and 6) expressed the folate receptor (FR-alpha) and 6 (INT.Ov1, 2, 5, 6, 7 and 9) expressed the epidermal growth factor receptor (EGFR); MAGE-1 and p185HER-2/neu were only found in 2 lines (INT.Ov1 and 2) and GAGE-1 expression in 1 line (INT.Ov2).
607 9334822 The identification of class I MHC ligands and T-cell epitopes within protein antigens was achieved by applying several theoretical methods including: 1) similarity or homology searches to MHCPEP; 2) BIMAS and 3) artificial neural network-based predictions of proteins MAGE, GAGE, EGFR, p185HER-2/neu and FR-alpha expressed in INT.Ov lines.
608 9334822 Notably all lines expressed HLA class I, intercellular adhesion molecule-1 (ICAM-1), polymorphic epithelial mucin (PEM) and cytokeratin (CK), but not HLA class II, B7.1 (CD80) or BAGE.
609 9334822 While of the 9 lines tested 4 (INT.Ov1, 2, 5 and 6) expressed the folate receptor (FR-alpha) and 6 (INT.Ov1, 2, 5, 6, 7 and 9) expressed the epidermal growth factor receptor (EGFR); MAGE-1 and p185HER-2/neu were only found in 2 lines (INT.Ov1 and 2) and GAGE-1 expression in 1 line (INT.Ov2).
610 9334822 The identification of class I MHC ligands and T-cell epitopes within protein antigens was achieved by applying several theoretical methods including: 1) similarity or homology searches to MHCPEP; 2) BIMAS and 3) artificial neural network-based predictions of proteins MAGE, GAGE, EGFR, p185HER-2/neu and FR-alpha expressed in INT.Ov lines.
611 9339848 Fractionation of CT120 TCLs into highly purified CD4+ and CD8+ T cell subsets demonstrated that the CD8+ T cell fraction mediated the suppressor effector function.
612 9339848 HLA restriction analysis revealed a complex pattern as both anti-HLA class II DR and anti-HLA class I (A, B, C) MAbs inhibited proliferation of oligoclonal CD8+ CT120 TCLs.
613 9342362 A challenge for subunit vaccines whose goal is to elicit CD8(+) cytotoxic T lymphocytes (CTLs) is to deliver the antigen to the cytosol of the living cell, where it can be processed for presentation by major histocompatibility complex (MHC) class I molecules.
614 9342362 To test whether the lethal factor protein could be exploited for delivery of exogenous proteins to the MHC class I processing pathway, we constructed a genetic fusion between the amino-terminal 254 aa of LF and the gp120 portion of the HIV-1 envelope protein.
615 9342362 A challenge for subunit vaccines whose goal is to elicit CD8(+) cytotoxic T lymphocytes (CTLs) is to deliver the antigen to the cytosol of the living cell, where it can be processed for presentation by major histocompatibility complex (MHC) class I molecules.
616 9342362 To test whether the lethal factor protein could be exploited for delivery of exogenous proteins to the MHC class I processing pathway, we constructed a genetic fusion between the amino-terminal 254 aa of LF and the gp120 portion of the HIV-1 envelope protein.
617 9371814 Mice immunized with heat shock proteins (hsps) isolated from mouse tumor cells (donor cells) produce CD8 cytotoxic T lymphocytes (CTL) that recognize donor cell peptides in association with the major histocompatibility complex (MHC) class I proteins of the responding mouse.
618 9371814 The CTL are induced apparently because peptides noncovalently associated with the isolated hsp molecules can enter the MHC class I antigen processing pathway of professional antigen-presenting cells.
619 9371814 Because large protein fragments or whole proteins serving as fusion partners can be cleaved into short peptides in the MHC class I processing pathway, hsp fusion proteins of the type described here are promising candidates for vaccines aimed at eliciting CD8 CTL in populations of MHC-disparate individuals.
620 9371814 Mice immunized with heat shock proteins (hsps) isolated from mouse tumor cells (donor cells) produce CD8 cytotoxic T lymphocytes (CTL) that recognize donor cell peptides in association with the major histocompatibility complex (MHC) class I proteins of the responding mouse.
621 9371814 The CTL are induced apparently because peptides noncovalently associated with the isolated hsp molecules can enter the MHC class I antigen processing pathway of professional antigen-presenting cells.
622 9371814 Because large protein fragments or whole proteins serving as fusion partners can be cleaved into short peptides in the MHC class I processing pathway, hsp fusion proteins of the type described here are promising candidates for vaccines aimed at eliciting CD8 CTL in populations of MHC-disparate individuals.
623 9371814 Mice immunized with heat shock proteins (hsps) isolated from mouse tumor cells (donor cells) produce CD8 cytotoxic T lymphocytes (CTL) that recognize donor cell peptides in association with the major histocompatibility complex (MHC) class I proteins of the responding mouse.
624 9371814 The CTL are induced apparently because peptides noncovalently associated with the isolated hsp molecules can enter the MHC class I antigen processing pathway of professional antigen-presenting cells.
625 9371814 Because large protein fragments or whole proteins serving as fusion partners can be cleaved into short peptides in the MHC class I processing pathway, hsp fusion proteins of the type described here are promising candidates for vaccines aimed at eliciting CD8 CTL in populations of MHC-disparate individuals.
626 9380724 The T1 helper peptide from the HIV-1 envelope protein was made more immunogenic for inducing T cell proliferation to the native sequence by replacing a residue that exerts an adverse influence on peptide binding to an MHC class II molecule.
627 9389743 In mice, human MUC1 is highly immunogenic, particularly when conjugated to mannan, where a high frequency of CD8(+) MHC-restricted cytotoxic T lymphocytes is induced, accompanied by tumor protection.
628 9419428 A novel MHC heterodimer, HLA-DM, facilitates the binding and presentation of peptides by class II DR, DP, and DQ molecules.
629 9445041 In two macaques immunized with a mixture of lipopeptides derived from simian immunodeficiency virus (SIV) Nef and Gag proteins, CTL responses were directed against the same, single epitope of the Nef protein (amino acids 128 to 137) presenting an alanine at position 136 (Nef 128-137/136A).
630 9445041 Dose analysis of peptides used to sensitize target cells as well as a major histocompatibility complex (MHC)-peptide stability assay suggested that the selected peptide Nef 128-137/136T has an altered capacity to bind to the MHC.
631 9448699 To evaluate an antigen delivery system in which exogenous antigen can target the major histocompatibility complex (MHC) class I pathway, a single human papillomavirus (HPV) 16 E7 cytotoxic T lymphocyte (CTL) epitope and a single HIV gp160 CTL epitope were separately fused to the C-terminus of bovine papillomavirus 1 (BPV1) L1 sequence to form hybrid BPV1L1 VLPs.
632 9448699 These data demonstrate that hybrid BPV1L1 VLPs can be used as carriers to target antigenic epitopes to both the MHC class I and class II pathways, providing a promising strategy for the design of vaccines to prevent virus infection, with the potential to elicit therapeutic virus-specific CTL responses.
633 9448699 To evaluate an antigen delivery system in which exogenous antigen can target the major histocompatibility complex (MHC) class I pathway, a single human papillomavirus (HPV) 16 E7 cytotoxic T lymphocyte (CTL) epitope and a single HIV gp160 CTL epitope were separately fused to the C-terminus of bovine papillomavirus 1 (BPV1) L1 sequence to form hybrid BPV1L1 VLPs.
634 9448699 These data demonstrate that hybrid BPV1L1 VLPs can be used as carriers to target antigenic epitopes to both the MHC class I and class II pathways, providing a promising strategy for the design of vaccines to prevent virus infection, with the potential to elicit therapeutic virus-specific CTL responses.
635 9456434 The antimetastatic effect of peptide pulsed APC could be further enhanced by pretreating the cells with antisense oligonucleotides directed against the TAP-2 gene to increase the density of specific peptide-major histocompatibility complex (MHC) class I complexes and thereby improve the APC function of the treated cells (Nair SK et al., J Immunol 1996;156:1772).
636 9469433 HLA-A*0201-restricted Melan-A-specific CTL recognize primarily the Melan-A(27-35) (AAGIGILTV) and the Melan-A(26-35) (EAAGIGILTV) peptides.
637 9469433 Surprisingly, analogues of the Melan-A(27-35) peptide, which bound more efficiently than the natural nonapeptide to HLA-A*0201, were poorly recognized by tumor-reactive CTL.
638 9469433 These results suggest that the Melan-A(26-35) peptide analogue ELAGIGILTV may be more immunogenic than the natural peptides in HLA-A*0201 melanoma patients and should thus be considered as a candidate for future peptide-based vaccine trials.
639 9469433 HLA-A*0201-restricted Melan-A-specific CTL recognize primarily the Melan-A(27-35) (AAGIGILTV) and the Melan-A(26-35) (EAAGIGILTV) peptides.
640 9469433 Surprisingly, analogues of the Melan-A(27-35) peptide, which bound more efficiently than the natural nonapeptide to HLA-A*0201, were poorly recognized by tumor-reactive CTL.
641 9469433 These results suggest that the Melan-A(26-35) peptide analogue ELAGIGILTV may be more immunogenic than the natural peptides in HLA-A*0201 melanoma patients and should thus be considered as a candidate for future peptide-based vaccine trials.
642 9469433 HLA-A*0201-restricted Melan-A-specific CTL recognize primarily the Melan-A(27-35) (AAGIGILTV) and the Melan-A(26-35) (EAAGIGILTV) peptides.
643 9469433 Surprisingly, analogues of the Melan-A(27-35) peptide, which bound more efficiently than the natural nonapeptide to HLA-A*0201, were poorly recognized by tumor-reactive CTL.
644 9469433 These results suggest that the Melan-A(26-35) peptide analogue ELAGIGILTV may be more immunogenic than the natural peptides in HLA-A*0201 melanoma patients and should thus be considered as a candidate for future peptide-based vaccine trials.
645 9480979 This study shows that induction of tumor-specific CD4+ T cells by vaccination with a specific viral T helper epitope, contained within a synthetic peptide, results in protective immunity against major histocompatibility complex (MHC) class II negative, virus-induced tumor cells.
646 9485028 The Her-2/neu oncogene encodes a Mr 185,000 transmembrane protein with homology to the epidermal growth factor receptor.
647 9485028 CTLs induced with DCs generated in the presence of TNF-alpha elicited a higher cytotoxic activity when they were stimulated with the cognate peptide than did CTLs induced with DCs grown in granulocyte macrophage colony-stimulating factor and interleukin 4 alone.
648 9485028 Furthermore, these CTLs lysed, in a MHC- and antigen-restricted fashion, not only breast cancer cells but also colon carcinoma and RCC cell lines expressing Her-2/neu.
649 9485027 These data show that HPV16 E7 protein-pulsed DCs, as well as the administration of E7 protein antigen in adjuvant, can effectively stimulate tumor-specific MHC class I-restricted CD8+ T-cell-mediated protective immunity to HPV16-induced cancers.
650 9497491 The expression of major histocompatibility complex (MHC) class II and B 7.2 (CD86) antigens on dendritic cells was significantly lower in transgenic mice compared with the same from the normal mice (P < 0.05).
651 9497491 Treatment of transgenic mice with interferon-gamma (IFN-gamma) resulted in up-regulation of MHC class II on dendritic cells, and lymphocytes from HBsAg-injected transgenic mice produced anti-HBs in vitro when cultured with dendritic cells from IFN-gamma-treated transgenic mice, but not when cultured with the dendritic cells from untreated transgenic mice.
652 9497491 Production of anti-HBs by lymphocytes from HBsAg-injected transgenic mice in the presence of dendritic cells that express higher levels of MHC class II and CD86 antigens has inspired optimism that a more effective vaccine therapy can be developed for chronic HBV-carriers, injecting vaccine containing HBsAg with modulator(s) of APC function of dendritic cells.
653 9497491 The expression of major histocompatibility complex (MHC) class II and B 7.2 (CD86) antigens on dendritic cells was significantly lower in transgenic mice compared with the same from the normal mice (P < 0.05).
654 9497491 Treatment of transgenic mice with interferon-gamma (IFN-gamma) resulted in up-regulation of MHC class II on dendritic cells, and lymphocytes from HBsAg-injected transgenic mice produced anti-HBs in vitro when cultured with dendritic cells from IFN-gamma-treated transgenic mice, but not when cultured with the dendritic cells from untreated transgenic mice.
655 9497491 Production of anti-HBs by lymphocytes from HBsAg-injected transgenic mice in the presence of dendritic cells that express higher levels of MHC class II and CD86 antigens has inspired optimism that a more effective vaccine therapy can be developed for chronic HBV-carriers, injecting vaccine containing HBsAg with modulator(s) of APC function of dendritic cells.
656 9497491 The expression of major histocompatibility complex (MHC) class II and B 7.2 (CD86) antigens on dendritic cells was significantly lower in transgenic mice compared with the same from the normal mice (P < 0.05).
657 9497491 Treatment of transgenic mice with interferon-gamma (IFN-gamma) resulted in up-regulation of MHC class II on dendritic cells, and lymphocytes from HBsAg-injected transgenic mice produced anti-HBs in vitro when cultured with dendritic cells from IFN-gamma-treated transgenic mice, but not when cultured with the dendritic cells from untreated transgenic mice.
658 9497491 Production of anti-HBs by lymphocytes from HBsAg-injected transgenic mice in the presence of dendritic cells that express higher levels of MHC class II and CD86 antigens has inspired optimism that a more effective vaccine therapy can be developed for chronic HBV-carriers, injecting vaccine containing HBsAg with modulator(s) of APC function of dendritic cells.
659 9498746 To identify shared epitopes for melanoma-reactive CTL restricted by MHC molecules other than HLA-A*0201, six human melanoma patient CTL lines expressing HLA-A1 were screened for reactivity against the melanocyte differentiation proteins Pmel-17/gp100, MART-1/Melan-A, and tyrosinase, expressed via recombinant vaccinia virus vectors.
660 9498757 Further, the inhibitory effect of mIEC was not restored by antibodies to TGF-beta, CD1d, E-cadherin, or MHC class I or II.
661 9498757 This inhibitory effect was noted for both gammadelta and alphabeta T cell subsets from IELs, and mRNA levels were reduced for both Th1 (IL-2 and IFN-gamma) and Th2 (IL-4 and IL-5) cytokines in gammadelta and alphabeta IELs.
662 9498770 Characterization of the interactions between MHC class I subunits: a systematic approach for the engineering of higher affinity variants of beta 2-microglobulin.
663 9515809 Interleukin 12 gene therapy of MHC-negative murine melanoma metastases.
664 9515809 In situ hybridization with cytokine probes detected a strong increase in the proportion of leukocytes positive for IFN-gamma, tumor necrosis factor alpha, IL-1beta, and IFN-inducible protein 10 at the site of rejection of IL-12-engineered tumor cells.
665 9515809 In conclusion, tumor therapy based on IL-12 gene transduction was effective on a MHC-negative metastatic tumor, suggesting a possible application to MHC-defective human neoplasms.
666 9515809 Interleukin 12 gene therapy of MHC-negative murine melanoma metastases.
667 9515809 In situ hybridization with cytokine probes detected a strong increase in the proportion of leukocytes positive for IFN-gamma, tumor necrosis factor alpha, IL-1beta, and IFN-inducible protein 10 at the site of rejection of IL-12-engineered tumor cells.
668 9515809 In conclusion, tumor therapy based on IL-12 gene transduction was effective on a MHC-negative metastatic tumor, suggesting a possible application to MHC-defective human neoplasms.
669 9532575 The expression vectors used to date have encoded antigens from several different viruses as well as a tumor-specific protein, an MHC class I molecule and a parasite antigen.
670 9551367 We have evaluated the abilities of a series of defined synthetic peptide epitopes derived from MART-1/Melan-A, gp100, tyrosinase, and MAGE-3 or unfractionated peptides naturally presented by melanoma MHC molecules to elicit HLA-A2-restricted and melanoma-reactive CTLs from the peripheral blood of normal donors or patients with metastatic melanoma.
671 9551367 Autologous peripheral blood dendritic cells (DCs), which were easily generated from all donors when cultured in the presence of recombinant human interleukin-4 and recombinant human granulocyte-macrophage colony-stimulating factor were pulsed with melanoma peptides and used to "prime" and/or "boost" CTL cultures in vitro.
672 9551367 Our results suggest that antimelanoma CTLs may be reproducibly generated in short-term in vitro cultures in this manner using either a subset of the defined synthetic peptides (MART-1/Melan-A27-35, MART-1/Melan-A32-40, gp100(280-288), tyrosinase368-376, and MAGE-3(271-279)) or unfractionated peptides (containing both idiotypic and shared melanoma epitopes) derived from freshly isolated autologous melanoma lesions.
673 9559973 Protective immunity against mycobacteria is dependent on antigen/MHC class II specific, CD4+ Th1 cells.
674 9559978 In this pathway, macrophages are required for processing the chaperoned peptides to make stable molecules with the major histocompatibility complex (MHC) class I molecules, even when HSP-peptide complexes are exogenously administered.
675 9559978 Through this pathway, vaccination with HSP-peptide complexes is thus able to elicit the response of CD8+ T cells specific for the chaperoned peptides.
676 9562688 MHC class I binding assays, of peptides derived from these proteins, demonstrated the presence of potential CD8+ T-cell epitopes.
677 9566494 All of the CD4+ T cell clones tested, displayed MHC class II restricted cytotoxicity against macrophages pulsed with M. tuberculosis.
678 9576612 Previous experiments showed that peptides corresponding to a major CD4-binding site on the beta2 domain of MHC class II molecules, IAbeta134-148, enhance responses by CD4+ T lymphocytes to antigen, allo-antigen and bacterial superantigen in vitro, and to soluble protein in vivo.
679 9576612 The results reported here suggest that participation of the T cell co-receptor, CD4, in TCR signaling differentially affected both T cell migration and the induction of antigen-specific tolerance.
680 9581906 Enhanced tumor protection by granulocyte-macrophage colony-stimulating factor expression at the site of an allogeneic vaccine.
681 9581906 Here we describe a series of experiments that directly examines the effects of allogeneic MHC molecules on the immune-priming capabilities of a whole cell tumor vaccine engineered to secrete GM-CSF.
682 9581906 In addition, allogeneic MHC expression has no inhibitory effect on the ability of GM-CSF-transduced vaccines to induce systemic antitumor immunity.
683 9581906 Enhanced tumor protection by granulocyte-macrophage colony-stimulating factor expression at the site of an allogeneic vaccine.
684 9581906 Here we describe a series of experiments that directly examines the effects of allogeneic MHC molecules on the immune-priming capabilities of a whole cell tumor vaccine engineered to secrete GM-CSF.
685 9581906 In addition, allogeneic MHC expression has no inhibitory effect on the ability of GM-CSF-transduced vaccines to induce systemic antitumor immunity.
686 9593013 The use of HLA-mismatched targets showed killing to be restricted by both HLA class I and class II antigens, although CD8-mediated class I cytotoxicity predominated.
687 9618870 Spleen cells from rFPV-gB inoculated chickens (MHC: B19B19), depleted for CD4+, CD8+, TCR gamma delta+, TCR alpha beta 1+ or TCR alpha beta 2+ cells were used as effector cells in chromium release assays.
688 9618870 Effector cells depleted of CD8+ or TCR alpha beta 1+, but not CD4+, TCR gamma delta+ or TCR alpha beta 2+ markedly reduced the percentage of specific release (%SR).
689 9620217 Involvement of MHC class I molecule and ICAM-1 in the enhancement of adhesion and cytotoxic susceptibility to immune effector cells of tumor cells transfected with the interleukin (IL)-2, IL-4 or IL-6 gene.
690 9620217 To investigate the molecular and cellular mechanisms involved in the reduced tumorigenicity and increased immunogenicity of interleukin-2 (IL-2)-, IL-4- or IL-6-gene-transfected B16 melanoma vaccine, we have analyzed the functional and phenotypic properties of these genetically engineered melanoma cells in the present study.
691 9620217 Using fluorescence-activated cell sorting analysis, we found that both MHC class I and ICAM-1 expression were increased after IL-2, IL-4 or IL-6 gene transfection.
692 9620217 These results suggested that the decreased tumorigenicity of IL-2-, IL- 4-, and IL-6-gene-transfected B16 melanoma cells may be partly due to the increased sensitivity to effector cell cytotoxicity mediated by increased expression of ICAM-1 or MHC class I molecules on the tumor cell surface after cytokine gene transfection.
693 9620217 Involvement of MHC class I molecule and ICAM-1 in the enhancement of adhesion and cytotoxic susceptibility to immune effector cells of tumor cells transfected with the interleukin (IL)-2, IL-4 or IL-6 gene.
694 9620217 To investigate the molecular and cellular mechanisms involved in the reduced tumorigenicity and increased immunogenicity of interleukin-2 (IL-2)-, IL-4- or IL-6-gene-transfected B16 melanoma vaccine, we have analyzed the functional and phenotypic properties of these genetically engineered melanoma cells in the present study.
695 9620217 Using fluorescence-activated cell sorting analysis, we found that both MHC class I and ICAM-1 expression were increased after IL-2, IL-4 or IL-6 gene transfection.
696 9620217 These results suggested that the decreased tumorigenicity of IL-2-, IL- 4-, and IL-6-gene-transfected B16 melanoma cells may be partly due to the increased sensitivity to effector cell cytotoxicity mediated by increased expression of ICAM-1 or MHC class I molecules on the tumor cell surface after cytokine gene transfection.
697 9625825 In all vaccines, all tumour cells expressed HLA class I, some expressed HLA class II and none expressed CD80.
698 9637487 Recent studies have reported that APC can present particulate exogenous Ag in the context of class I MHC to CD8+ CTL, and our laboratory demonstrated that IL-3 could enhance CTL generation to exogenous Ag.
699 9637761 At 48 h, most of the MF59 at the site of injection was inside cells that were immunoreactive for the dendritic cell markers DEC-205 and MHC class II molecules, reflecting the interaction of MF59 with antigen presenting cells.
700 9637766 After four to five weekly stimulations of bulk PBLs with DC/gp100 or DC/lysates, the cultures were enriched with CD3+ T-cells and exhibited one of three phenotypic and functional patterns: (1) Predominant expression of CD8+ and MHC class I-restricted CTLs which displayed strong lytic activity against melanoma cells and T2 cells loaded with the gp100 peptide, (2) mixed CD4+/CD8+ phenotype and weak lytic activity, or (3) nonlytic and predominantly CD4+ cultures.
701 9640250 Gene transfer of costimulatory molecules into a human colorectal cancer cell line: requirement of CD54, CD80 and class II MHC expression for enhanced immunogenicity.
702 9640250 Using transfected variants of the human colorectal cancer cell line SW480 we tested various costimulatory molecules (CD80, CD86, CD54) and a class II major histocompatibility complex (MHC) allele (HLA-DR3) alone or in combination on their ability to support primary T-lymphocyte activation in vitro.
703 9640250 Expression of CD80 or CD86 similarly as the combination of both was not sufficient to induce proliferation of human allogeneic T cells.
704 9640250 Expression of CD54 together with CD80 strongly augmented the costimulatory function of CD80, as observed in the presence of a CD3 monoclonal antibody (mAb), but did not lead directly to a T-cell response against modified tumour cells.
705 9640250 Importantly, SW480 cells coexpressing CD54, CD80 and the HLA-DR3 allele effectively promoted T-lymphocyte proliferation.
706 9640250 Moreover, the use of such CD54+/CD80+/HLA-DR3+ SW480 variants for repetitive stimulations resulted in the generation of T-cell lines predominantly composed of CD8+ T cells exhibiting class I MHC restricted cytolytic activity towards untransfected SW480 tumour cells.
707 9640250 Gene transfer of costimulatory molecules into a human colorectal cancer cell line: requirement of CD54, CD80 and class II MHC expression for enhanced immunogenicity.
708 9640250 Using transfected variants of the human colorectal cancer cell line SW480 we tested various costimulatory molecules (CD80, CD86, CD54) and a class II major histocompatibility complex (MHC) allele (HLA-DR3) alone or in combination on their ability to support primary T-lymphocyte activation in vitro.
709 9640250 Expression of CD80 or CD86 similarly as the combination of both was not sufficient to induce proliferation of human allogeneic T cells.
710 9640250 Expression of CD54 together with CD80 strongly augmented the costimulatory function of CD80, as observed in the presence of a CD3 monoclonal antibody (mAb), but did not lead directly to a T-cell response against modified tumour cells.
711 9640250 Importantly, SW480 cells coexpressing CD54, CD80 and the HLA-DR3 allele effectively promoted T-lymphocyte proliferation.
712 9640250 Moreover, the use of such CD54+/CD80+/HLA-DR3+ SW480 variants for repetitive stimulations resulted in the generation of T-cell lines predominantly composed of CD8+ T cells exhibiting class I MHC restricted cytolytic activity towards untransfected SW480 tumour cells.
713 9640250 Gene transfer of costimulatory molecules into a human colorectal cancer cell line: requirement of CD54, CD80 and class II MHC expression for enhanced immunogenicity.
714 9640250 Using transfected variants of the human colorectal cancer cell line SW480 we tested various costimulatory molecules (CD80, CD86, CD54) and a class II major histocompatibility complex (MHC) allele (HLA-DR3) alone or in combination on their ability to support primary T-lymphocyte activation in vitro.
715 9640250 Expression of CD80 or CD86 similarly as the combination of both was not sufficient to induce proliferation of human allogeneic T cells.
716 9640250 Expression of CD54 together with CD80 strongly augmented the costimulatory function of CD80, as observed in the presence of a CD3 monoclonal antibody (mAb), but did not lead directly to a T-cell response against modified tumour cells.
717 9640250 Importantly, SW480 cells coexpressing CD54, CD80 and the HLA-DR3 allele effectively promoted T-lymphocyte proliferation.
718 9640250 Moreover, the use of such CD54+/CD80+/HLA-DR3+ SW480 variants for repetitive stimulations resulted in the generation of T-cell lines predominantly composed of CD8+ T cells exhibiting class I MHC restricted cytolytic activity towards untransfected SW480 tumour cells.
719 9658070 CD8(+) T lymphocytes from immunized animals were able to potently suppress SIV replication in autologous SIV-infected CD4(+) T cells.
720 9658070 Suppression of SIV replication by unstimulated CD8(+) T cells required direct contact and was major histocompatibility complex (MHC) restricted.
721 9658070 However, CD3-stimulated CD8(+) T cells produced soluble factors that inhibited SIV replication in an MHC-unrestricted fashion as much as 30-fold.
722 9658070 Supernatants from stimulated CD8(+) T cells were also able to inhibit replication of both CCR5- and CXCR4-dependent human immunodeficiency virus type 1 (HIV-1) strains.
723 9658070 Production of RANTES, macrophage inhibitory protein 1alpha (MIP-1alpha), or MIP-1beta from stimulated CD8(+) T cells of vaccinated animals was almost 10-fold higher than that from stimulated CD8(+) T cells of control animals.
724 9658070 Our results indicate that inhibition of SIV replication by CD8(+) T cells from animals immunized with live attenuated SIV strains involves both MHC-restricted and -unrestricted mechanisms and that MHC-unrestricted inhibition of SIV replication is due principally to soluble factors other than RANTES, MIP-1alpha, and MIP-1beta.
725 9658070 CD8(+) T lymphocytes from immunized animals were able to potently suppress SIV replication in autologous SIV-infected CD4(+) T cells.
726 9658070 Suppression of SIV replication by unstimulated CD8(+) T cells required direct contact and was major histocompatibility complex (MHC) restricted.
727 9658070 However, CD3-stimulated CD8(+) T cells produced soluble factors that inhibited SIV replication in an MHC-unrestricted fashion as much as 30-fold.
728 9658070 Supernatants from stimulated CD8(+) T cells were also able to inhibit replication of both CCR5- and CXCR4-dependent human immunodeficiency virus type 1 (HIV-1) strains.
729 9658070 Production of RANTES, macrophage inhibitory protein 1alpha (MIP-1alpha), or MIP-1beta from stimulated CD8(+) T cells of vaccinated animals was almost 10-fold higher than that from stimulated CD8(+) T cells of control animals.
730 9658070 Our results indicate that inhibition of SIV replication by CD8(+) T cells from animals immunized with live attenuated SIV strains involves both MHC-restricted and -unrestricted mechanisms and that MHC-unrestricted inhibition of SIV replication is due principally to soluble factors other than RANTES, MIP-1alpha, and MIP-1beta.
731 9658070 CD8(+) T lymphocytes from immunized animals were able to potently suppress SIV replication in autologous SIV-infected CD4(+) T cells.
732 9658070 Suppression of SIV replication by unstimulated CD8(+) T cells required direct contact and was major histocompatibility complex (MHC) restricted.
733 9658070 However, CD3-stimulated CD8(+) T cells produced soluble factors that inhibited SIV replication in an MHC-unrestricted fashion as much as 30-fold.
734 9658070 Supernatants from stimulated CD8(+) T cells were also able to inhibit replication of both CCR5- and CXCR4-dependent human immunodeficiency virus type 1 (HIV-1) strains.
735 9658070 Production of RANTES, macrophage inhibitory protein 1alpha (MIP-1alpha), or MIP-1beta from stimulated CD8(+) T cells of vaccinated animals was almost 10-fold higher than that from stimulated CD8(+) T cells of control animals.
736 9658070 Our results indicate that inhibition of SIV replication by CD8(+) T cells from animals immunized with live attenuated SIV strains involves both MHC-restricted and -unrestricted mechanisms and that MHC-unrestricted inhibition of SIV replication is due principally to soluble factors other than RANTES, MIP-1alpha, and MIP-1beta.
737 9659229 Preservation of mucosal and systemic adjuvant properties of ISCOMS in the absence of functional interleukin-4 or interferon-gamma.
738 9659229 Here we have investigated whether interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) are required for the induction of local and systemic immune responses by oral and parenteral administration of ovalbumin (OVA) in immune stimulating complexes (ISCOMS), a potent mucosal adjuvant vector.
739 9659229 Our results show that after oral or systemic immunization with OVA ISCOMS, IL-4 knockout (IL4KO) and IFN-gamma receptor knockout (IFN-gamma RKO) mice develop an entirely normal range of immune responses including delayed-type hypersensitivity (DTH), serum immunoglobulin G (IgG) antibodies, T-cell proliferation and cytokine production, class I major histocompatibility complex (MHC)-restricted cytotoxic T lymphocyte (CTL) activity and intestinal IgA antibodies.
740 9659229 These responses were of a similar magnitude to those found in the wild-type mice, indicating that the immunogenicity of ISCOMS is not influenced by the presence of IL-4 or IFN-gamma and emphasizing the potential of ISCOMS as widely applicable mucosal adjuvants.
741 9664146 Inhibition of murine melanoma growth by granulocyte-macrophage colony stimulating factor gene transfection is not haplotype specific.
742 9664146 Granulocyte-macrophage colony stimulating factor (GM-CSF) has been shown to inhibit the growth and progression of murine melanoma cells in syngeneic C57BL/6 (H-2b) recipient animals.
743 9664146 Thus, these studies demonstrate for the first time that GM-CSF inhibits melanoma growth in a second genetically distinct MHC tumour-host model system and further support the use of GM-CSF in clinical trials in the treatment of advanced malignant melanoma in humans.
744 9667667 Analysis of the autologous tumour cell vaccines regarding IL-7 secretion after gene transfer, HLA class I and class II cell surface expression, secretion of immunosuppressive mediators (TGF-beta1, IL-10) and various melanoma-associated tumour antigens revealed a very diverse expression profile.
745 9670040 Although a recombinant vaccinia virus (rVV) encoding the mouse homologue of gp100 was nonimmunogenic, immunization of normal C57BL/6 mice with the rVV encoding the human gp100 elicited a specific CD8(+) T cell response.
746 9670040 The ability to induce specific T cells with human but not mouse gp100 resulted from differences within the major histocompatibility complex (MHC) class I-restricted epitope and not from differences elsewhere in the molecule, as was evidenced by experiments in which mice were immunized with rVV containing minigenes encoding these epitopes.
747 9682342 At different time points post-vaccination, the induction of HBsAg specific, MHC-I-restricted CD8+ T cells and of serum antibodies to HBsAg was monitored.
748 9686182 Studies using MHC class I and class II knockout mice infected with B. abortus have demonstrated that protective immunity to brucellosis is especially dependent on CD8+ T cells.
749 9686639 Cross-clade envelope glycoprotein 160-specific CD8+ cytotoxic T lymphocyte responses in early HIV type 1 clade B infection.
750 9686639 A major objective of current HIV-1 vaccination strategies is the induction of HIV-1-specific CD8+ MHC class I-restricted CTL responses, which are suggested to play a pivotal role in viral clearance and protection against HIV-1 disease progression.
751 9699670 We report here a novel formula of hydrophobized polysaccharide nanoparticles, which can deliver a HER2 oncoprotein containing an epitope peptide to the MHC class I pathway.
752 9699670 CHM-HER2 and CHP-HER2 were able to induce CD3+/CD8+ CTLs against HER2-transfected syngeneic fibrosarcoma cell lines.
753 9725236 CD8+ T cells derived from HLA-A*0201+ patients with active tuberculosis (TB) as well as tuberculin skin test-positive individuals who had no history of TB were used as effector cells to determine whether these epitopes are recognized by in vivo-primed CTLs.
754 9725236 An in vitro vaccination system using HLA-A*0201+ dendritic cells (DCs) as APCs was used to determine whether these epitopes can sensitize naive CD8+ T cells in vitro, leading to the generation of Ag-specific CTLs.
755 9725236 The results show that an HLA-A*0201-binding peptide comprised of residues 88 to 97 of M.tb19 (P88-97) is recognized by circulating CD8+ CTLs from both healthy tuberculin skin test-positive individuals and patients with active TB but not by tuberculin skin test-negative subjects.
756 9725236 CD8+ T cells derived from HLA-A*0201+ patients with active tuberculosis (TB) as well as tuberculin skin test-positive individuals who had no history of TB were used as effector cells to determine whether these epitopes are recognized by in vivo-primed CTLs.
757 9725236 An in vitro vaccination system using HLA-A*0201+ dendritic cells (DCs) as APCs was used to determine whether these epitopes can sensitize naive CD8+ T cells in vitro, leading to the generation of Ag-specific CTLs.
758 9725236 The results show that an HLA-A*0201-binding peptide comprised of residues 88 to 97 of M.tb19 (P88-97) is recognized by circulating CD8+ CTLs from both healthy tuberculin skin test-positive individuals and patients with active TB but not by tuberculin skin test-negative subjects.
759 9725236 CD8+ T cells derived from HLA-A*0201+ patients with active tuberculosis (TB) as well as tuberculin skin test-positive individuals who had no history of TB were used as effector cells to determine whether these epitopes are recognized by in vivo-primed CTLs.
760 9725236 An in vitro vaccination system using HLA-A*0201+ dendritic cells (DCs) as APCs was used to determine whether these epitopes can sensitize naive CD8+ T cells in vitro, leading to the generation of Ag-specific CTLs.
761 9725236 The results show that an HLA-A*0201-binding peptide comprised of residues 88 to 97 of M.tb19 (P88-97) is recognized by circulating CD8+ CTLs from both healthy tuberculin skin test-positive individuals and patients with active TB but not by tuberculin skin test-negative subjects.
762 9737670 In this study, we show that proinflammatory stimuli induce the expression of other cytokines such as IL-6, transforming growth factor-beta (TGF-beta), and granulocyte-macrophage colony-stimulating factor (GM-CSF) by muscle cells themselves, as well as the up-regulation of human leucocyte antigen (HLA) class I, class II and intercellular adhesion molecule-1 (ICAM-1).
763 9737670 The levels of HLA class I, class II and ICAM-1 in inflamed muscle may be affected by the secreted products of the stimulation.
764 9737670 In this study, we show that proinflammatory stimuli induce the expression of other cytokines such as IL-6, transforming growth factor-beta (TGF-beta), and granulocyte-macrophage colony-stimulating factor (GM-CSF) by muscle cells themselves, as well as the up-regulation of human leucocyte antigen (HLA) class I, class II and intercellular adhesion molecule-1 (ICAM-1).
765 9737670 The levels of HLA class I, class II and ICAM-1 in inflamed muscle may be affected by the secreted products of the stimulation.
766 9743387 Previous studies have shown that two 10-mer PSA peptides (designated PSA-1 and PSA-3) selected to conform to human HLA class I-A2 motifs can elicit CTL responses in vitro.
767 9743387 A longer PSA peptide (30-mer) designated PSA-OP (oligoepitope peptide), which contains both the PSA-1 and PSA-3 HLA-A2 epitopes and an additional potential CTL epitope (designated PSA-9) for the HLA-class I-A3 allele, was investigated for the ability to induce cytotoxic T cell activity.
768 9743387 Previous studies have shown that two 10-mer PSA peptides (designated PSA-1 and PSA-3) selected to conform to human HLA class I-A2 motifs can elicit CTL responses in vitro.
769 9743387 A longer PSA peptide (30-mer) designated PSA-OP (oligoepitope peptide), which contains both the PSA-1 and PSA-3 HLA-A2 epitopes and an additional potential CTL epitope (designated PSA-9) for the HLA-class I-A3 allele, was investigated for the ability to induce cytotoxic T cell activity.
770 9743520 A p53 hotspot mutation at amino acid position 273 from R to H, flanking a peptide epitope that spans residues 264-272, renders cells resistant to killing by human histocompatibility leukocyte antigen (HLA)-A*0201-restricted cytotoxic T lymphocytes (CTLs) specific for this epitope.
771 9748126 CTL specificity was measured by IFN-gamma release assay using HLA-A*0201 matched target cells.
772 9757942 The presentation of antigenic peptides by major histocompatibility complex (MHC) class II to CD4+ T cells is crucial to initiate immune responses.
773 9757942 Mouse L cell transfectants expressing either of these two mutated Ii along with HLA-DR4 could process and present M12p55-68 to the peptide specific and DR4-restricted CD4+ T cell clone.
774 9757942 These results indicate that the peptide substituted for CLIP of Ii p33 bound to the groove of DR molecules in the same manner as CLIP and it was preferentially presented to the CD4+ T cell clone in the absence of HLA-DM molecules.
775 9774275 Responses were directed against all 10 peptides tested and were restricted by six human lymphocyte antigen (HLA) class I alleles.
776 9784506 DNA vaccination was evaluated with the experimental murine model of Trypanosoma cruzi infection as a means to induce antiparasite protective immunity, and the trypomastigote surface antigen 1 (TSA-1), a target of anti-T. cruzi antibody and major histocompatibility complex (MHC) class I-restricted CD8(+) cytotoxic T-lymphocyte (CTL) responses, was used as the model antigen.
777 9784506 In H-2(d) mice, inoculation with either of the two TSA-1-expressing vectors effectively generated antiparasite antibodies and primed CTLs that lysed T. cruzi-infected cells in an antigen-specific, MHC class I-restricted, and CD8(+)-T-cell-dependent manner.
778 9784506 DNA vaccination was evaluated with the experimental murine model of Trypanosoma cruzi infection as a means to induce antiparasite protective immunity, and the trypomastigote surface antigen 1 (TSA-1), a target of anti-T. cruzi antibody and major histocompatibility complex (MHC) class I-restricted CD8(+) cytotoxic T-lymphocyte (CTL) responses, was used as the model antigen.
779 9784506 In H-2(d) mice, inoculation with either of the two TSA-1-expressing vectors effectively generated antiparasite antibodies and primed CTLs that lysed T. cruzi-infected cells in an antigen-specific, MHC class I-restricted, and CD8(+)-T-cell-dependent manner.
780 9807734 Anchor residues in cytotoxic T-lymphocyte (CTL) epitope-bearing peptides are buried deep in the major histocompatibility complex (MHC) class I antigen-presenting groove and are essential for binding to MHC class I molecules.
781 9816208 Lack of T-cell-mediated recognition of the fusion region of the pml/RAR-alpha hybrid protein by lymphocytes of acute promyelocytic leukemia patients.
782 9816208 In previous studies, it was shown that the fusion region of the pml/RAR-alpha protein, expressed by acute promyelocytic leukemia (APL) cells, can be specifically recognized in vitro by donor (D.
783 9816208 G.) with BCR1/25, a 25-mer pml/RAR-alpha, did not elicit either a polyclonal or a clonal immune response specific to the peptide.
784 9816208 We then generated new donor anti-pml/RAR-alpha CD4(+) T-cell clones.
785 9816208 One clone (C3/5, CD3(+), CD4(+), CD8(-)) was selected for further analysis.
786 9816208 Clone C3/5 showed specific proliferation, cytotoxicity, and cytokine (tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor) production when challenged with autologous lymphoblastic cell lines pulsed with peptide BCR1/25.
787 9816208 G. whether the use of 9-mer peptides (BCR1/9) would generate a CD8/HLA class I-restricted response.
788 9816214 Specific CD8(+) CTL recognition of melanoma requires expression of MHC class I molecules as well as melanoma-associated peptide epitopes.
789 9816214 Stable MHC class I cell surface expression requires delivery of cytosolic peptides into the endoplasmic reticulum by the peptide transporter molecules TAP1 and TAP2, with peptides subsequently transported to the cell surface in complexes containing MHC class I heavy chain and beta2-microglobulin.
790 9816214 We have evaluated a series of mechanisms resulting in MHC class I down-regulation in a human melanoma cell line, Mz18, typed as HLA-A2(+), A3(+), B7(+), B57(+), Cw1(+), and Cw6(+) by genomic PCR analysis.
791 9816214 The melanoma cell line Mz18 exhibits a global down-regulation of MHC class I heavy chain transcripts; beta2-microglobulin; the proteasome subunits LMP2/7, involved in generating cytosolic peptide fragments; and the peptide transporter molecules TAP1 and TAP2, involved in peptide transport from the cytosol into the endoplasmic reticulum.
792 9816214 IFN-gamma treatment of Mz18 melanoma cells leads to up-regulation of LMP2/7 and TAP1/2, as well as to up-regulation of HLA-B and HLA-C MHC loci alleles, but not HLA-A2 or HLA-A3.
793 9816214 Melanoma peptides could only be presented and recognized by CTLs if the HLA-A2-transfected Mz18 cell line was first treated with IFN-gamma, thereby restoring LMP2/7 and TAP1/2 expression and function.
794 9816214 Because several melanoma antigens recognized by T cells have been reported to be presented by HLA-A2 (MART-1/Melan-A, tyrosinase, gp100, and MAGE-3), the loss of HLA-A2 molecules may represent an important mechanism by which many melanomas evade immune recognition.
795 9816214 These findings suggest that patients entering clinical trials for immunotherapy with melanoma vaccines should be carefully examined for tumor cell allelic MHC class I loss and whether such MHC class I antigen down-regulation can be restored by cytokines.
796 9816214 Specific CD8(+) CTL recognition of melanoma requires expression of MHC class I molecules as well as melanoma-associated peptide epitopes.
797 9816214 Stable MHC class I cell surface expression requires delivery of cytosolic peptides into the endoplasmic reticulum by the peptide transporter molecules TAP1 and TAP2, with peptides subsequently transported to the cell surface in complexes containing MHC class I heavy chain and beta2-microglobulin.
798 9816214 We have evaluated a series of mechanisms resulting in MHC class I down-regulation in a human melanoma cell line, Mz18, typed as HLA-A2(+), A3(+), B7(+), B57(+), Cw1(+), and Cw6(+) by genomic PCR analysis.
799 9816214 The melanoma cell line Mz18 exhibits a global down-regulation of MHC class I heavy chain transcripts; beta2-microglobulin; the proteasome subunits LMP2/7, involved in generating cytosolic peptide fragments; and the peptide transporter molecules TAP1 and TAP2, involved in peptide transport from the cytosol into the endoplasmic reticulum.
800 9816214 IFN-gamma treatment of Mz18 melanoma cells leads to up-regulation of LMP2/7 and TAP1/2, as well as to up-regulation of HLA-B and HLA-C MHC loci alleles, but not HLA-A2 or HLA-A3.
801 9816214 Melanoma peptides could only be presented and recognized by CTLs if the HLA-A2-transfected Mz18 cell line was first treated with IFN-gamma, thereby restoring LMP2/7 and TAP1/2 expression and function.
802 9816214 Because several melanoma antigens recognized by T cells have been reported to be presented by HLA-A2 (MART-1/Melan-A, tyrosinase, gp100, and MAGE-3), the loss of HLA-A2 molecules may represent an important mechanism by which many melanomas evade immune recognition.
803 9816214 These findings suggest that patients entering clinical trials for immunotherapy with melanoma vaccines should be carefully examined for tumor cell allelic MHC class I loss and whether such MHC class I antigen down-regulation can be restored by cytokines.
804 9816214 Specific CD8(+) CTL recognition of melanoma requires expression of MHC class I molecules as well as melanoma-associated peptide epitopes.
805 9816214 Stable MHC class I cell surface expression requires delivery of cytosolic peptides into the endoplasmic reticulum by the peptide transporter molecules TAP1 and TAP2, with peptides subsequently transported to the cell surface in complexes containing MHC class I heavy chain and beta2-microglobulin.
806 9816214 We have evaluated a series of mechanisms resulting in MHC class I down-regulation in a human melanoma cell line, Mz18, typed as HLA-A2(+), A3(+), B7(+), B57(+), Cw1(+), and Cw6(+) by genomic PCR analysis.
807 9816214 The melanoma cell line Mz18 exhibits a global down-regulation of MHC class I heavy chain transcripts; beta2-microglobulin; the proteasome subunits LMP2/7, involved in generating cytosolic peptide fragments; and the peptide transporter molecules TAP1 and TAP2, involved in peptide transport from the cytosol into the endoplasmic reticulum.
808 9816214 IFN-gamma treatment of Mz18 melanoma cells leads to up-regulation of LMP2/7 and TAP1/2, as well as to up-regulation of HLA-B and HLA-C MHC loci alleles, but not HLA-A2 or HLA-A3.
809 9816214 Melanoma peptides could only be presented and recognized by CTLs if the HLA-A2-transfected Mz18 cell line was first treated with IFN-gamma, thereby restoring LMP2/7 and TAP1/2 expression and function.
810 9816214 Because several melanoma antigens recognized by T cells have been reported to be presented by HLA-A2 (MART-1/Melan-A, tyrosinase, gp100, and MAGE-3), the loss of HLA-A2 molecules may represent an important mechanism by which many melanomas evade immune recognition.
811 9816214 These findings suggest that patients entering clinical trials for immunotherapy with melanoma vaccines should be carefully examined for tumor cell allelic MHC class I loss and whether such MHC class I antigen down-regulation can be restored by cytokines.
812 9816214 Specific CD8(+) CTL recognition of melanoma requires expression of MHC class I molecules as well as melanoma-associated peptide epitopes.
813 9816214 Stable MHC class I cell surface expression requires delivery of cytosolic peptides into the endoplasmic reticulum by the peptide transporter molecules TAP1 and TAP2, with peptides subsequently transported to the cell surface in complexes containing MHC class I heavy chain and beta2-microglobulin.
814 9816214 We have evaluated a series of mechanisms resulting in MHC class I down-regulation in a human melanoma cell line, Mz18, typed as HLA-A2(+), A3(+), B7(+), B57(+), Cw1(+), and Cw6(+) by genomic PCR analysis.
815 9816214 The melanoma cell line Mz18 exhibits a global down-regulation of MHC class I heavy chain transcripts; beta2-microglobulin; the proteasome subunits LMP2/7, involved in generating cytosolic peptide fragments; and the peptide transporter molecules TAP1 and TAP2, involved in peptide transport from the cytosol into the endoplasmic reticulum.
816 9816214 IFN-gamma treatment of Mz18 melanoma cells leads to up-regulation of LMP2/7 and TAP1/2, as well as to up-regulation of HLA-B and HLA-C MHC loci alleles, but not HLA-A2 or HLA-A3.
817 9816214 Melanoma peptides could only be presented and recognized by CTLs if the HLA-A2-transfected Mz18 cell line was first treated with IFN-gamma, thereby restoring LMP2/7 and TAP1/2 expression and function.
818 9816214 Because several melanoma antigens recognized by T cells have been reported to be presented by HLA-A2 (MART-1/Melan-A, tyrosinase, gp100, and MAGE-3), the loss of HLA-A2 molecules may represent an important mechanism by which many melanomas evade immune recognition.
819 9816214 These findings suggest that patients entering clinical trials for immunotherapy with melanoma vaccines should be carefully examined for tumor cell allelic MHC class I loss and whether such MHC class I antigen down-regulation can be restored by cytokines.
820 9816214 Specific CD8(+) CTL recognition of melanoma requires expression of MHC class I molecules as well as melanoma-associated peptide epitopes.
821 9816214 Stable MHC class I cell surface expression requires delivery of cytosolic peptides into the endoplasmic reticulum by the peptide transporter molecules TAP1 and TAP2, with peptides subsequently transported to the cell surface in complexes containing MHC class I heavy chain and beta2-microglobulin.
822 9816214 We have evaluated a series of mechanisms resulting in MHC class I down-regulation in a human melanoma cell line, Mz18, typed as HLA-A2(+), A3(+), B7(+), B57(+), Cw1(+), and Cw6(+) by genomic PCR analysis.
823 9816214 The melanoma cell line Mz18 exhibits a global down-regulation of MHC class I heavy chain transcripts; beta2-microglobulin; the proteasome subunits LMP2/7, involved in generating cytosolic peptide fragments; and the peptide transporter molecules TAP1 and TAP2, involved in peptide transport from the cytosol into the endoplasmic reticulum.
824 9816214 IFN-gamma treatment of Mz18 melanoma cells leads to up-regulation of LMP2/7 and TAP1/2, as well as to up-regulation of HLA-B and HLA-C MHC loci alleles, but not HLA-A2 or HLA-A3.
825 9816214 Melanoma peptides could only be presented and recognized by CTLs if the HLA-A2-transfected Mz18 cell line was first treated with IFN-gamma, thereby restoring LMP2/7 and TAP1/2 expression and function.
826 9816214 Because several melanoma antigens recognized by T cells have been reported to be presented by HLA-A2 (MART-1/Melan-A, tyrosinase, gp100, and MAGE-3), the loss of HLA-A2 molecules may represent an important mechanism by which many melanomas evade immune recognition.
827 9816214 These findings suggest that patients entering clinical trials for immunotherapy with melanoma vaccines should be carefully examined for tumor cell allelic MHC class I loss and whether such MHC class I antigen down-regulation can be restored by cytokines.
828 9816214 Specific CD8(+) CTL recognition of melanoma requires expression of MHC class I molecules as well as melanoma-associated peptide epitopes.
829 9816214 Stable MHC class I cell surface expression requires delivery of cytosolic peptides into the endoplasmic reticulum by the peptide transporter molecules TAP1 and TAP2, with peptides subsequently transported to the cell surface in complexes containing MHC class I heavy chain and beta2-microglobulin.
830 9816214 We have evaluated a series of mechanisms resulting in MHC class I down-regulation in a human melanoma cell line, Mz18, typed as HLA-A2(+), A3(+), B7(+), B57(+), Cw1(+), and Cw6(+) by genomic PCR analysis.
831 9816214 The melanoma cell line Mz18 exhibits a global down-regulation of MHC class I heavy chain transcripts; beta2-microglobulin; the proteasome subunits LMP2/7, involved in generating cytosolic peptide fragments; and the peptide transporter molecules TAP1 and TAP2, involved in peptide transport from the cytosol into the endoplasmic reticulum.
832 9816214 IFN-gamma treatment of Mz18 melanoma cells leads to up-regulation of LMP2/7 and TAP1/2, as well as to up-regulation of HLA-B and HLA-C MHC loci alleles, but not HLA-A2 or HLA-A3.
833 9816214 Melanoma peptides could only be presented and recognized by CTLs if the HLA-A2-transfected Mz18 cell line was first treated with IFN-gamma, thereby restoring LMP2/7 and TAP1/2 expression and function.
834 9816214 Because several melanoma antigens recognized by T cells have been reported to be presented by HLA-A2 (MART-1/Melan-A, tyrosinase, gp100, and MAGE-3), the loss of HLA-A2 molecules may represent an important mechanism by which many melanomas evade immune recognition.
835 9816214 These findings suggest that patients entering clinical trials for immunotherapy with melanoma vaccines should be carefully examined for tumor cell allelic MHC class I loss and whether such MHC class I antigen down-regulation can be restored by cytokines.
836 9822287 Blood-derived DC up-regulated MHC class II, CD54, CD80 and CD86 after exposure to WV vaccine, indicating their functional maturation, but were only moderately affected by subunit (SU) vaccines.
837 9822287 The production of IL-2 and interferon-gamma (IFN-gamma) by PBMC was also strongly stimulated by WV, but much less by SU vaccines, among which the v-SU vaccine was a better stimulator of IL-2 secretion.
838 9833768 Primary human mesothelioma cells express class II MHC, ICAM-1 and B7-2 and can present recall antigens to autologous blood lymphocytes.
839 9833768 Intercellular adhesion molecule-I (ICAM-I; CD54); class I and class II major histocompatibility complex-DR (MHCI and MHCII-DR); B7-1 (CD80.3); and B7-2 (CD86) expression by MMc was studied by immunocytochemical and/or FACScan analysis.
840 9848223 Major histocompatibility complex (MHC) class I antigen is a potent stimulus for alloimmune responses and is the principal immunologic target mediating acute cellular rejection of allografts.
841 9848223 Specifically, coimmunization with IL-10 cDNA abrogated immunity to allo-MHC class I, while coimmunization with GM-CSF cDNA enhanced it.
842 9848681 Isolation of recombinant phage clones expressing mycobacterial T cell antigens by screening a recombinant DNA library with human CD4+ Th1 clones.
843 9848681 Pools of recombinant antigens from 12 wells were tested in T cell proliferation assays with MHC class II restricted human CD4+ Th1 clones secreting interferon-gamma and cytotoxic for antigen pulsed antigen presenting cells.
844 9862730 Diversity of the fine specificity displayed by HLA-A*0201-restricted CTL specific for the immunodominant Melan-A/MART-1 antigenic peptide.
845 9862730 HLA-A*0201 melanoma patients often develop a CTL response to an immunodominant peptide derived from the melanocyte lineage-specific protein Melan-A/MART-1.
846 9862730 To substantiate this observation, we have now tested a series of Melan-A(26-35) variant peptides containing single alanine substitutions for binding to HLA-A*0201 and recognition by polyclonal and monoclonal Melan-A-specific CTL.
847 9862730 Diversity of the fine specificity displayed by HLA-A*0201-restricted CTL specific for the immunodominant Melan-A/MART-1 antigenic peptide.
848 9862730 HLA-A*0201 melanoma patients often develop a CTL response to an immunodominant peptide derived from the melanocyte lineage-specific protein Melan-A/MART-1.
849 9862730 To substantiate this observation, we have now tested a series of Melan-A(26-35) variant peptides containing single alanine substitutions for binding to HLA-A*0201 and recognition by polyclonal and monoclonal Melan-A-specific CTL.
850 9862730 Diversity of the fine specificity displayed by HLA-A*0201-restricted CTL specific for the immunodominant Melan-A/MART-1 antigenic peptide.
851 9862730 HLA-A*0201 melanoma patients often develop a CTL response to an immunodominant peptide derived from the melanocyte lineage-specific protein Melan-A/MART-1.
852 9862730 To substantiate this observation, we have now tested a series of Melan-A(26-35) variant peptides containing single alanine substitutions for binding to HLA-A*0201 and recognition by polyclonal and monoclonal Melan-A-specific CTL.
853 9862732 HLA-independent heterogeneity of CD8+ T cell responses to MAGE-3, Melan-A/MART-1, gp100, tyrosinase, MC1R, and TRP-2 in vaccine-treated melanoma patients.
854 9862732 To identify such peptides, we evaluated HLA-A*02+ melanoma patients immunized to a polyvalent vaccine containing multiple Ags, including MAGE-3, Melan-A/MART-1, gp100, tyrosinase, melanocortin receptor (MC1R), and dopachrome tautomerase (TRP-2).
855 9862732 Using a filter spot assay, we measured peripheral blood CD8+ T cell responses, before and after immunization, to a panel of 45 HLA-A*0201-restricted peptides derived from these Ags.
856 9862732 HLA-independent heterogeneity of CD8+ T cell responses to MAGE-3, Melan-A/MART-1, gp100, tyrosinase, MC1R, and TRP-2 in vaccine-treated melanoma patients.
857 9862732 To identify such peptides, we evaluated HLA-A*02+ melanoma patients immunized to a polyvalent vaccine containing multiple Ags, including MAGE-3, Melan-A/MART-1, gp100, tyrosinase, melanocortin receptor (MC1R), and dopachrome tautomerase (TRP-2).
858 9862732 Using a filter spot assay, we measured peripheral blood CD8+ T cell responses, before and after immunization, to a panel of 45 HLA-A*0201-restricted peptides derived from these Ags.
859 9864234 Populations of T-cell-receptor (TCR) alphabeta+ CD4(+) CD54(+) cells localized to gastric tissue of immunized C57BL/6 wild-type and MHC class I knockout mice, but TCRalphabeta+ CD8(+) cells predominated in the gastric tissue of immunized MHC class II-deficient mice.
860 9864234 These observations show that CD4(+) T cells engaged after mucosal immunization may be important for the generation of a protective anti-H. pylori immune response and that CD4(+) CD8(-) and CD4(-) CD8(+) T cells regulate the extent of H. pylori infection in vivo.
861 9885899 These peptides exhibited high binding affinity for HLA-A*0201 molecules and stimulated CD8+ T cells of relatively limited TCR Vbeta chain repertoire.
862 9930305 In this study we describe the generation and characterization of replication incompetent herpes simplex virus type 1 (HSV-1) vectors (HX86Z or HX86G) carrying distinct and independently regulated expression cassettes for five transgenes (hIL-2, hGM-CSF, hB7.1, HSV-tk and lacZ or hIFN gamma).
863 9930305 Deletion of the immediate--early genes ICP4, ICP22 and ICP27 substantially reduced vector cytotoxicity, prevented early and late viral gene expression and left intact MHC class I antigen expression.
864 9934701 This study demonstrates the capacity of both Th and CTL activated peptide vaccines to elicit CD8+, MHC class I-restricted CTLs.
865 9973436 A hsp70-2 mutation recognized by CTL on a human renal cell carcinoma.
866 9973436 This TCRBV6J1S1 CTL recognized only the autologous RCC-7 tumor cell line in the context of HLA-A*0201, and the Ag is encoded by a mutated form of the hsp70-2 gene found in the tumor cells, but not in autologous PBLs nor in 47 other tumors.
867 9973436 The finding in the tumor of a mutated form of the stress-induced hsp70-2 gene whose product is specifically recognized by TILs with high avidity is discussed in view of the present use of mycobacteria or heterologous heat-shock proteins as immunomodulators or as subunit vaccine candidates.
868 10048391 CD8+ cytotoxic T lymphocyte (CTL) activity was generated that recognized a dominant "tumor-specific" major histocompatibility complex (MHC) class I-restricted epitope (AH1) from CT26 cells.
869 10065631 These microbes primarily stimulate CD4 T-cells via antigen presentation through MHC class II molecules.
870 10065631 This 'cytoplasmic' pathogen is controlled by CD8 T-cells through MHC class I antigen presentation.
871 10065631 Some bacterial pathogens such as Mycobacterium tuberculosis presumably remain in the phagosome but apparently 'perforate' the phagosomal membrane and thus stimulate both CD4 and CD8 T-cells.
872 10065631 Such constructs are capable of introducing antigens into the MHC class II and MHC class I pathway, resulting in stimulation of both CD4 and CD8 T-cells.
873 10065631 These microbes primarily stimulate CD4 T-cells via antigen presentation through MHC class II molecules.
874 10065631 This 'cytoplasmic' pathogen is controlled by CD8 T-cells through MHC class I antigen presentation.
875 10065631 Some bacterial pathogens such as Mycobacterium tuberculosis presumably remain in the phagosome but apparently 'perforate' the phagosomal membrane and thus stimulate both CD4 and CD8 T-cells.
876 10065631 Such constructs are capable of introducing antigens into the MHC class II and MHC class I pathway, resulting in stimulation of both CD4 and CD8 T-cells.
877 10065631 These microbes primarily stimulate CD4 T-cells via antigen presentation through MHC class II molecules.
878 10065631 This 'cytoplasmic' pathogen is controlled by CD8 T-cells through MHC class I antigen presentation.
879 10065631 Some bacterial pathogens such as Mycobacterium tuberculosis presumably remain in the phagosome but apparently 'perforate' the phagosomal membrane and thus stimulate both CD4 and CD8 T-cells.
880 10065631 Such constructs are capable of introducing antigens into the MHC class II and MHC class I pathway, resulting in stimulation of both CD4 and CD8 T-cells.
881 10067674 Major histocompatibility complex (MHC) class I molecules present endogenously derived viral peptides to CD8+ cytotoxic T-lymphocytes (CTLs).
882 10068264 Strategies to overcome this include up-regulation of MHC and introduction of cell adhesion molecules into tumor cells, suppression of transforming growth factor and interleukin 10 production by tumor cells, and blockade of the fas ligand-fas interaction between tumor cells and attacking lymphocytes.
883 10084964 In contrast, ZP2(121-140) peptide elicited antibody in inbred mice with three additional mouse MHC haplotypes.
884 10092812 Resistance to the mouse pneumonitis (MoPn) strain of Chlamydia trachomatis has been mapped to MHC class II-restricted, IL-12-dependent CD4+ T cells that secrete a type 1 profile of proinflammatory cytokines, which includes IFN-gamma and TNF-alpha.
885 10092815 Assessment of immunogenicity of human Melan-A peptide analogues in HLA-A*0201/Kb transgenic mice.
886 10092815 Previous studies have shown that substitution of single amino acid residues in human Melan-A immunodominant peptides Melan-A27-35 and Melan-A26-35 greatly improved their binding and the stability of peptide/HLA-A*0201 complexes.
887 10092815 In this study, we analyzed the in vivo immunogenicity of Melan-A natural peptides and their analogues in HLA-A*0201/Kb transgenic mice.
888 10092815 More interestingly, these mouse CTL were also able to lyse human melanoma cell lines in vitro in a HLA-A*0201-restricted, Melan-A-specific manner.
889 10092815 Our results indicate that the HLA-A*0201/Kb transgenic mouse is a useful animal model to perform preclinical testing of potential cancer vaccines, and that Melan-A peptide analogues are attractive candidates for melanoma immunotherapy.
890 10092815 Assessment of immunogenicity of human Melan-A peptide analogues in HLA-A*0201/Kb transgenic mice.
891 10092815 Previous studies have shown that substitution of single amino acid residues in human Melan-A immunodominant peptides Melan-A27-35 and Melan-A26-35 greatly improved their binding and the stability of peptide/HLA-A*0201 complexes.
892 10092815 In this study, we analyzed the in vivo immunogenicity of Melan-A natural peptides and their analogues in HLA-A*0201/Kb transgenic mice.
893 10092815 More interestingly, these mouse CTL were also able to lyse human melanoma cell lines in vitro in a HLA-A*0201-restricted, Melan-A-specific manner.
894 10092815 Our results indicate that the HLA-A*0201/Kb transgenic mouse is a useful animal model to perform preclinical testing of potential cancer vaccines, and that Melan-A peptide analogues are attractive candidates for melanoma immunotherapy.
895 10092815 Assessment of immunogenicity of human Melan-A peptide analogues in HLA-A*0201/Kb transgenic mice.
896 10092815 Previous studies have shown that substitution of single amino acid residues in human Melan-A immunodominant peptides Melan-A27-35 and Melan-A26-35 greatly improved their binding and the stability of peptide/HLA-A*0201 complexes.
897 10092815 In this study, we analyzed the in vivo immunogenicity of Melan-A natural peptides and their analogues in HLA-A*0201/Kb transgenic mice.
898 10092815 More interestingly, these mouse CTL were also able to lyse human melanoma cell lines in vitro in a HLA-A*0201-restricted, Melan-A-specific manner.
899 10092815 Our results indicate that the HLA-A*0201/Kb transgenic mouse is a useful animal model to perform preclinical testing of potential cancer vaccines, and that Melan-A peptide analogues are attractive candidates for melanoma immunotherapy.
900 10092815 Assessment of immunogenicity of human Melan-A peptide analogues in HLA-A*0201/Kb transgenic mice.
901 10092815 Previous studies have shown that substitution of single amino acid residues in human Melan-A immunodominant peptides Melan-A27-35 and Melan-A26-35 greatly improved their binding and the stability of peptide/HLA-A*0201 complexes.
902 10092815 In this study, we analyzed the in vivo immunogenicity of Melan-A natural peptides and their analogues in HLA-A*0201/Kb transgenic mice.
903 10092815 More interestingly, these mouse CTL were also able to lyse human melanoma cell lines in vitro in a HLA-A*0201-restricted, Melan-A-specific manner.
904 10092815 Our results indicate that the HLA-A*0201/Kb transgenic mouse is a useful animal model to perform preclinical testing of potential cancer vaccines, and that Melan-A peptide analogues are attractive candidates for melanoma immunotherapy.
905 10092815 Assessment of immunogenicity of human Melan-A peptide analogues in HLA-A*0201/Kb transgenic mice.
906 10092815 Previous studies have shown that substitution of single amino acid residues in human Melan-A immunodominant peptides Melan-A27-35 and Melan-A26-35 greatly improved their binding and the stability of peptide/HLA-A*0201 complexes.
907 10092815 In this study, we analyzed the in vivo immunogenicity of Melan-A natural peptides and their analogues in HLA-A*0201/Kb transgenic mice.
908 10092815 More interestingly, these mouse CTL were also able to lyse human melanoma cell lines in vitro in a HLA-A*0201-restricted, Melan-A-specific manner.
909 10092815 Our results indicate that the HLA-A*0201/Kb transgenic mouse is a useful animal model to perform preclinical testing of potential cancer vaccines, and that Melan-A peptide analogues are attractive candidates for melanoma immunotherapy.
910 10187808 Tumor antigens presented by major histocompatibility complex (MHC) class I molecules and recognized by CD8(+) cytotoxic T lymphocytes (CTLs) may generate an efficient antitumor immune response after appropriate immunization.
911 10205916 The disseminated disease in DCL patients is resistant to chemotherapy, and is characterized by a Th2 cytokine pattern, with a an absence of IL-2 AND ifn-gamma production when the lymphocytes are specifically stimulated by leishmanial antigen.
912 10205916 The epidermis of LCL lesions show ICAM-1 in patches and MHC uniformly expressed by keratinocytes.
913 10205916 DCL lesions are characterized by low CD4/CD8 and memory/naive T cell ratios, low numbers of T gamma delta cells, and an apparent defect in the expression of LFA-1 directional receptors.
914 10205916 MCL granulomas manifest high CD4/CD8 and memory/naive Tcel ratios, low numbers of T gamma delta, a high coefficients of cellular adhesion, with a mixed Th1/Th2 cytokine pattern.
915 10205916 LCL granulomas are characterized by a normal CD4/CD8 ratio, a high memory/naive cell ratio, numerous groups of T gamma delta, a high expression of directional receptors, and Th1/Th0 cytokine patterns.
916 10223336 It has been postulated that upon binding to a cell surface receptor, papilloma virus-like particles (VLPs) gain entry into the cytosol of infected cells and the capsid proteins L1 and L2 can be processed in the MHC class I presentation pathway.
917 10223336 The vigorous response was specific for VLP-infected target cells and was MHC class I restricted.
918 10223336 Moreover we show the presence of at least one HLA-A*0201 restricted CTL epitope within the HPV-16 capsid proteins by using a VLP-'infected' HLA-A*0201 transfected human cell line as target cells.
919 10223336 It has been postulated that upon binding to a cell surface receptor, papilloma virus-like particles (VLPs) gain entry into the cytosol of infected cells and the capsid proteins L1 and L2 can be processed in the MHC class I presentation pathway.
920 10223336 The vigorous response was specific for VLP-infected target cells and was MHC class I restricted.
921 10223336 Moreover we show the presence of at least one HLA-A*0201 restricted CTL epitope within the HPV-16 capsid proteins by using a VLP-'infected' HLA-A*0201 transfected human cell line as target cells.
922 10223336 It has been postulated that upon binding to a cell surface receptor, papilloma virus-like particles (VLPs) gain entry into the cytosol of infected cells and the capsid proteins L1 and L2 can be processed in the MHC class I presentation pathway.
923 10223336 The vigorous response was specific for VLP-infected target cells and was MHC class I restricted.
924 10223336 Moreover we show the presence of at least one HLA-A*0201 restricted CTL epitope within the HPV-16 capsid proteins by using a VLP-'infected' HLA-A*0201 transfected human cell line as target cells.
925 10228017 T cell responses to Gram-negative intracellular bacterial pathogens: a role for CD8+ T cells in immunity to Salmonella infection and the involvement of MHC class Ib molecules.
926 10229097 Several cancer immune intervention protocols aim at inducing T cell immunity against antigens presented by HLA-A2, the most common human MHC class I molecule.
927 10233683 Further study to find the mechanism underlying this revealed that there was up-regulation of major histocompatibility complex (MHC) class II, CD86 antigens on DC and increased production of interleukin-12 (IL-12) by DC and of IL-2, and tumour necrosis factor-alpha (TNF-alpha) in DC/T-cell cultures when vaccine containing HBsAg was injected in HBV-Tg with potent DC function but not in HBV-Tg with poor DC function.
928 10233743 In a murine model, we analysed the in vitro effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) alone or combined with interleukin-4 (IL-4) or Flt3 ligand (Flt3-L) on the number, immunophenotype and functions of bone marrow-derived DC.
929 10233743 In GM-CSF cultures, we have identified two populations based on their level of expression of major histocompatibility complex (MHC) class II molecules: MHC-IIhi cells, exhibiting the typical morphology and immunophenotype of myeloid DC (CD11c+ 33D1+ DEC-205+ F4/80+), and MHC-IIlo cells, heterogeneous for DC markers (30% CD11c+; 50% 33D1+; DEC-205-; F4/80+).
930 10233743 In contrast, after addition of IL-4 to GM-CSF, the two populations displayed a very similar phenotype (CD11c+ 33D1- DEC-205+ F4/80-), differing only in their expression levels of MHC class II and costimulatory molecules, and showed similar stimulatory activity in mixed leucocyte reaction.
931 10233743 In a murine model, we analysed the in vitro effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) alone or combined with interleukin-4 (IL-4) or Flt3 ligand (Flt3-L) on the number, immunophenotype and functions of bone marrow-derived DC.
932 10233743 In GM-CSF cultures, we have identified two populations based on their level of expression of major histocompatibility complex (MHC) class II molecules: MHC-IIhi cells, exhibiting the typical morphology and immunophenotype of myeloid DC (CD11c+ 33D1+ DEC-205+ F4/80+), and MHC-IIlo cells, heterogeneous for DC markers (30% CD11c+; 50% 33D1+; DEC-205-; F4/80+).
933 10233743 In contrast, after addition of IL-4 to GM-CSF, the two populations displayed a very similar phenotype (CD11c+ 33D1- DEC-205+ F4/80-), differing only in their expression levels of MHC class II and costimulatory molecules, and showed similar stimulatory activity in mixed leucocyte reaction.
934 10319257 The BoLA region is unlike the MHC of humans and mice in that a large inversion has moved several class II genes, including the TAP/LMP cluster, close to the centromere of bovine chromosome 23.
935 10328228 To direct recombinant ErbB-2 to the cytoplasm where major histocompatibility complex (MHC) I peptide processing takes place, the endoplasmic reticulum (ER) signal sequence was deleted in cyt ErbB-2.
936 10347750 Our objective was to determine the effect of IFN-gamma on transgene expression driven by viral SV40 or CMV promoter/enhancer and the mammalian promoter/enhancer for the major histocompatibility complex class I (MHC I) gene.
937 10347750 Luciferase assays of transfected cells untreated or treated with IFN-gamma indicated that although the viral promoters could drive luciferase production in all cell lines tested to higher or lower levels than the MHC I promoter, treatment with IFN-gamma inhibited transgene expression in most of the cell lines and amplification of the MHC I promoter-driven transgene expression in all cell lines.
938 10347750 Our objective was to determine the effect of IFN-gamma on transgene expression driven by viral SV40 or CMV promoter/enhancer and the mammalian promoter/enhancer for the major histocompatibility complex class I (MHC I) gene.
939 10347750 Luciferase assays of transfected cells untreated or treated with IFN-gamma indicated that although the viral promoters could drive luciferase production in all cell lines tested to higher or lower levels than the MHC I promoter, treatment with IFN-gamma inhibited transgene expression in most of the cell lines and amplification of the MHC I promoter-driven transgene expression in all cell lines.
940 10352284 Combination gene therapy with CD86 and the MHC class II transactivator in the control of lung tumor growth.
941 10352284 Early reports suggest that the costimulatory molecule CD86 (B7-2) has sporadic efficacy in tumor immunity, whereas changes in cancer immunity mediated by the MHC class II transactivator (CIITA) have not been extensively investigated.
942 10352284 CIITA activates MHC class II expression in most cells; however, in the Line 1 lung carcinoma model system, CIITA activates MHC class I and well as class II.
943 10352284 These data suggest that if CIITA and CD86 cooperate, enhanced tumor immunity could be achieved.
944 10352284 When CIITA and CD86 were coexpressed, there was no cooperative immune protection from tumor growth.
945 10352284 These data suggest that human cancer vaccine trials utilizing CIITA gene therapy alone or in combination with CD86 should be approached with caution.
946 10352308 Induction of HLA class I-restricted CD8+ CTLs specific for the major outer membrane protein of Chlamydia trachomatis in human genital tract infections.
947 10352308 HLA class I-restricted CD8+ CTLs specific for the major outer membrane protein (MOMP) of Chlamydia trachomatis are present in the peripheral blood of humans who acquired genital tract infections with the organism.
948 10352308 Induction of HLA class I-restricted CD8+ CTLs specific for the major outer membrane protein of Chlamydia trachomatis in human genital tract infections.
949 10352308 HLA class I-restricted CD8+ CTLs specific for the major outer membrane protein (MOMP) of Chlamydia trachomatis are present in the peripheral blood of humans who acquired genital tract infections with the organism.
950 10352317 Among HLA class I genes, A29 (p = 0.001) and B22 (p < 0.0001) are significantly associated with rapid progression, whereas B14 (p = 0.001) and C8 (p = 0.004) are significantly associated with nonprogression.
951 10361129 It was demonstrated that major histocompatibility complex (MHC)-unrestricted cytotoxic T cells can recognize epitopes of the MUC1 protein core localized in the tandem repeat domain.
952 10361129 There is increasing evidence now that MHC-restricted T cells can also be induced after immunization with the MUC1 protein or segments of the core tandem repeat.
953 10361129 The addition of a Pan-HLA-DR binding peptide PADRE as a T-helper epitope during the in vitro priming resulted in an increased cytotoxic activity of the MUC1-specific CTL and a higher production of cytokines such as interleukin-12 and interferon-gamma in the cell cultures, demonstrating the importance of CD4 cells for an efficient CTL priming.
954 10361129 It was demonstrated that major histocompatibility complex (MHC)-unrestricted cytotoxic T cells can recognize epitopes of the MUC1 protein core localized in the tandem repeat domain.
955 10361129 There is increasing evidence now that MHC-restricted T cells can also be induced after immunization with the MUC1 protein or segments of the core tandem repeat.
956 10361129 The addition of a Pan-HLA-DR binding peptide PADRE as a T-helper epitope during the in vitro priming resulted in an increased cytotoxic activity of the MUC1-specific CTL and a higher production of cytokines such as interleukin-12 and interferon-gamma in the cell cultures, demonstrating the importance of CD4 cells for an efficient CTL priming.
957 10363968 To study the induction of anti-"self" CD8+ T-cell reactivity against the tumor antigen gp100, we used a mouse transgenic for a chimeric HLA-A*0201/H-2 Kb molecule (A2/Kb).
958 10363968 Immunogens containing the "anchor-fixed" modification elicited anti-self CD8+ T cells specific for the wild-type gp100(209-217) peptide pulsed onto target cells.
959 10364497 High-yield reassortant influenza vaccine production virus has a mutation at an HLA-A 2.1-restricted CD8+ CTL epitope on the NS1 protein.
960 10364497 We established a human CD8(+) cytotoxic T cell (CTL) line, 10-2C2, which recognizes an HLA-A2.1-restricted influenza A virus H1, H2, H3 cross-reactive T cell epitope on amino acids 122-130 of the NS1 protein, and unexpectedly we observed that there was decreased lysis of target cells infected with the A/Texas/36/91 (H1N1) vaccine virus strain compared to the lysis of target cells infected with the prototype A/PR/8/34 (H1N1) virus.
961 10364497 Current influenza vaccines are inactivated and do not contain the NS1 protein; however, future influenza vaccines may include live attenuated vaccines and with this mutation a live virus would fail to induce a CD8(+) CTL response to this epitope in individuals with HLA-A2.1, a very common allele, and potentially have reduced efficacy.
962 10382603 In this context, CD4+ T-cells produce cytokines required for the clonal expansion of CTLs that kill their target cells in a major histocompatibility complex (MHC) class I-restricted manner.
963 10382603 In addition, CD4+ T-cells produce macrophage-activating cytokines such as IFN-gamma.
964 10382603 An effective vaccine must include schizont proteins, notably, those proteins that are secreted into the host cell cytoplasm because these may have access to the MHC class I and II compartments to be presented to CTLs and CD4+ T-cells, respectively.
965 10382603 In this context, CD4+ T-cells produce cytokines required for the clonal expansion of CTLs that kill their target cells in a major histocompatibility complex (MHC) class I-restricted manner.
966 10382603 In addition, CD4+ T-cells produce macrophage-activating cytokines such as IFN-gamma.
967 10382603 An effective vaccine must include schizont proteins, notably, those proteins that are secreted into the host cell cytoplasm because these may have access to the MHC class I and II compartments to be presented to CTLs and CD4+ T-cells, respectively.
968 10384115 A model for CD8+ CTL tumor immunosurveillance and regulation of tumor escape by CD4 T cells through an effect on quality of CTL.
969 10384115 Regression was dependent on CD8 T cells, and recurrent tumors were resistant to CTL, had substantially reduced expression of epitope mRNA, but retained the gp160 gene, MHC, and processing apparatus.
970 10384115 Unexpectedly, CD4 cell depletion protected mice from tumor recurrence, whereas IL-4 knockout mice, deficient in Th2 cells, did not show this protection, and IFN-gamma knockout mice were more susceptible.
971 10384115 Purified CD8 T cells from CD4-depleted mice following tumor regression had more IFN-gamma mRNA and lysed tumor cells without stimulation ex vivo, in contrast to CD4-intact mice.
972 10384115 Thus, the quality as well as quantity of CD8+ CTL determines the completeness of immunosurveillance and is controlled by CD4 T cells but not solely Th2 cytokines.
973 10386338 Additionally, a Nef-deleted SIV virus has low titres in rhesus monkeys and the animals develop AIDS at a much slower rate.
974 10386338 In vitro, Nef can exert at least three kinds of effects: it downregulates CD4 and MHC class I, it stimulates virion infectivity and it alters signal transduction pathways.
975 10386338 To accomplish this, Nef interacts with a series of cellular partners including CD4, components of the adaptor complexes AP-1 and AP-2, and several protein kinases, Nef often functioning as a connector between targets and effectors.
976 10417764 Mass-spectrometric evaluation of HLA-A*0201-associated peptides identifies dominant naturally processed forms of CTL epitopes from MART-1 and gp100.
977 10417764 Melanoma-reactive human cytotoxic T lymphocytes (CTLs) mediate tumor regression in vivo through specific recognition of MHC-associated peptide epitopes, many of which are encoded by the melanocytic tissue differentiation proteins gp100/Pme117 and MART-1/Melan-A.
978 10417764 Especially where these peptides may be used in human clinical trials for the treatment or prevention of cancer, there is substantial need for direct evaluation of HLA-A*0201-associated peptides from MART-1 and gp100 that are naturally processed and presented.
979 10417764 To that end, we have isolated peptides directly from HLA-A*0201 molecules of human melanoma cells and have determined that naturally processed epitopes for HLA-A*0201-restricted, melanoma-reactive CTLs include the nonamers MART-1(27-35) (AAGIGILTV), gp100(154-162) (KTWGQYWQV), gp100(209-217) (ITDQVPFSV) and gp100(280-288) (YLEPGPVTA) and the decamer gp100(476-485) (VLYRYGSFSV).
980 10417764 HLA-A*0201-restricted CTLs from one melanoma patient who has survived metastatic disease recognized MART-1(27-35) (AAGIGILTV), gp100(280-288) (YLEPGPVTA) and gp100(154-162) (KTWGQYWQV) and were cross-reactive on longer peptides that contained these nonamer sequences.
981 10417764 Mass-spectrometric evaluation of HLA-A*0201-associated peptides identifies dominant naturally processed forms of CTL epitopes from MART-1 and gp100.
982 10417764 Melanoma-reactive human cytotoxic T lymphocytes (CTLs) mediate tumor regression in vivo through specific recognition of MHC-associated peptide epitopes, many of which are encoded by the melanocytic tissue differentiation proteins gp100/Pme117 and MART-1/Melan-A.
983 10417764 Especially where these peptides may be used in human clinical trials for the treatment or prevention of cancer, there is substantial need for direct evaluation of HLA-A*0201-associated peptides from MART-1 and gp100 that are naturally processed and presented.
984 10417764 To that end, we have isolated peptides directly from HLA-A*0201 molecules of human melanoma cells and have determined that naturally processed epitopes for HLA-A*0201-restricted, melanoma-reactive CTLs include the nonamers MART-1(27-35) (AAGIGILTV), gp100(154-162) (KTWGQYWQV), gp100(209-217) (ITDQVPFSV) and gp100(280-288) (YLEPGPVTA) and the decamer gp100(476-485) (VLYRYGSFSV).
985 10417764 HLA-A*0201-restricted CTLs from one melanoma patient who has survived metastatic disease recognized MART-1(27-35) (AAGIGILTV), gp100(280-288) (YLEPGPVTA) and gp100(154-162) (KTWGQYWQV) and were cross-reactive on longer peptides that contained these nonamer sequences.
986 10417764 Mass-spectrometric evaluation of HLA-A*0201-associated peptides identifies dominant naturally processed forms of CTL epitopes from MART-1 and gp100.
987 10417764 Melanoma-reactive human cytotoxic T lymphocytes (CTLs) mediate tumor regression in vivo through specific recognition of MHC-associated peptide epitopes, many of which are encoded by the melanocytic tissue differentiation proteins gp100/Pme117 and MART-1/Melan-A.
988 10417764 Especially where these peptides may be used in human clinical trials for the treatment or prevention of cancer, there is substantial need for direct evaluation of HLA-A*0201-associated peptides from MART-1 and gp100 that are naturally processed and presented.
989 10417764 To that end, we have isolated peptides directly from HLA-A*0201 molecules of human melanoma cells and have determined that naturally processed epitopes for HLA-A*0201-restricted, melanoma-reactive CTLs include the nonamers MART-1(27-35) (AAGIGILTV), gp100(154-162) (KTWGQYWQV), gp100(209-217) (ITDQVPFSV) and gp100(280-288) (YLEPGPVTA) and the decamer gp100(476-485) (VLYRYGSFSV).
990 10417764 HLA-A*0201-restricted CTLs from one melanoma patient who has survived metastatic disease recognized MART-1(27-35) (AAGIGILTV), gp100(280-288) (YLEPGPVTA) and gp100(154-162) (KTWGQYWQV) and were cross-reactive on longer peptides that contained these nonamer sequences.
991 10417764 Mass-spectrometric evaluation of HLA-A*0201-associated peptides identifies dominant naturally processed forms of CTL epitopes from MART-1 and gp100.
992 10417764 Melanoma-reactive human cytotoxic T lymphocytes (CTLs) mediate tumor regression in vivo through specific recognition of MHC-associated peptide epitopes, many of which are encoded by the melanocytic tissue differentiation proteins gp100/Pme117 and MART-1/Melan-A.
993 10417764 Especially where these peptides may be used in human clinical trials for the treatment or prevention of cancer, there is substantial need for direct evaluation of HLA-A*0201-associated peptides from MART-1 and gp100 that are naturally processed and presented.
994 10417764 To that end, we have isolated peptides directly from HLA-A*0201 molecules of human melanoma cells and have determined that naturally processed epitopes for HLA-A*0201-restricted, melanoma-reactive CTLs include the nonamers MART-1(27-35) (AAGIGILTV), gp100(154-162) (KTWGQYWQV), gp100(209-217) (ITDQVPFSV) and gp100(280-288) (YLEPGPVTA) and the decamer gp100(476-485) (VLYRYGSFSV).
995 10417764 HLA-A*0201-restricted CTLs from one melanoma patient who has survived metastatic disease recognized MART-1(27-35) (AAGIGILTV), gp100(280-288) (YLEPGPVTA) and gp100(154-162) (KTWGQYWQV) and were cross-reactive on longer peptides that contained these nonamer sequences.
996 10417764 Mass-spectrometric evaluation of HLA-A*0201-associated peptides identifies dominant naturally processed forms of CTL epitopes from MART-1 and gp100.
997 10417764 Melanoma-reactive human cytotoxic T lymphocytes (CTLs) mediate tumor regression in vivo through specific recognition of MHC-associated peptide epitopes, many of which are encoded by the melanocytic tissue differentiation proteins gp100/Pme117 and MART-1/Melan-A.
998 10417764 Especially where these peptides may be used in human clinical trials for the treatment or prevention of cancer, there is substantial need for direct evaluation of HLA-A*0201-associated peptides from MART-1 and gp100 that are naturally processed and presented.
999 10417764 To that end, we have isolated peptides directly from HLA-A*0201 molecules of human melanoma cells and have determined that naturally processed epitopes for HLA-A*0201-restricted, melanoma-reactive CTLs include the nonamers MART-1(27-35) (AAGIGILTV), gp100(154-162) (KTWGQYWQV), gp100(209-217) (ITDQVPFSV) and gp100(280-288) (YLEPGPVTA) and the decamer gp100(476-485) (VLYRYGSFSV).
1000 10417764 HLA-A*0201-restricted CTLs from one melanoma patient who has survived metastatic disease recognized MART-1(27-35) (AAGIGILTV), gp100(280-288) (YLEPGPVTA) and gp100(154-162) (KTWGQYWQV) and were cross-reactive on longer peptides that contained these nonamer sequences.
1001 10418926 Mice immunised with oxidised mannan conjugated to the human mucin 1 (MUC1), produce MHC Class 1 restricted CD8+ cytotoxic T-cells which eradicate MUC1 + tumours, indicating potential for the immunotherapy of MUC1 + cancers in humans.
1002 10418926 High titred antibodies specific for MUC1 were produced, MUC1 specific CD4+ and CD8+ T-cell proliferative responses and specific cytotoxic precursor cells (CTLp) were found, but not MUC1 specific cytotoxic T-cells (CTL).
1003 10438922 Priming MHC-I-restricted cytotoxic T lymphocyte responses to exogenous hepatitis B surface antigen is CD4+ T cell dependent.
1004 10438922 Priming of this CTL response by exogenous HBsAg required CD4+ T cell "help" and IL-12: this CTL response could be neither induced in mice depleted of CD4+ T cells by in vivo Ab treatment, nor in (CD4+ T cell-competent or CD4+ T cell-depleted) IL-12-unresponsive STAT4-/- knockout BALB/c mice.
1005 10438922 In vivo priming of the well-characterized CD8+ CTL response to HBsAg in "high responder" BALB/c mice either by exogenous surface lipoprotein particles or by DNA vaccination is thus CD4+ T cell dependent.
1006 10445813 The CTLs were CD8+ and HLA class I restricted.
1007 10447932 In order to investigate the role of B7-1 and B7-2, the human RCC cell line, MZ1257RC, which expresses normal levels of adhesion molecules and major histocompatibility complex (MHC) class I surface antigens, was transfected with B7-1 and B7-2 expression vectors, respectively.
1008 10447932 In contrast, IL-2 only co-operatively increased T-cell activation in the presence of B7-2.
1009 10473111 By using a MHC-binding assay, eight peptides derived from MAGE-2 were found to bind with sufficient affinity to the HLA-A24 molecule.
1010 10473111 When the induction of specific cytotoxic T lymphocytes (CTLs) was examined using a simplified method, the highest human lymphocyte antigen (HLA) binder (EYLQLVFGI) in these peptides was able to elicit CTLs from unseparated peripheral blood mononuclear cells in HLA-A24 healthy donors by stimulation with freshly isolated, peptide-pulsed peripheral blood mononuclear cells as antigen-presenting cells and also by using interleukin 7 and keyhole-limpet hemocyanin in a primary culture.
1011 10473111 The induced CTL could, thus, lyse HLA-A24 tumor cells expressing MAGE-2, as well as the peptide-pulsed target cells, with antigen specificity in a HLA class I-restricted manner.
1012 10473111 By using a MHC-binding assay, eight peptides derived from MAGE-2 were found to bind with sufficient affinity to the HLA-A24 molecule.
1013 10473111 When the induction of specific cytotoxic T lymphocytes (CTLs) was examined using a simplified method, the highest human lymphocyte antigen (HLA) binder (EYLQLVFGI) in these peptides was able to elicit CTLs from unseparated peripheral blood mononuclear cells in HLA-A24 healthy donors by stimulation with freshly isolated, peptide-pulsed peripheral blood mononuclear cells as antigen-presenting cells and also by using interleukin 7 and keyhole-limpet hemocyanin in a primary culture.
1014 10473111 The induced CTL could, thus, lyse HLA-A24 tumor cells expressing MAGE-2, as well as the peptide-pulsed target cells, with antigen specificity in a HLA class I-restricted manner.
1015 10477566 DCs incubated with recombinant S. gordonii were much more efficient than DCs pulsed with soluble C-fragment of tetanus toxin at stimulating specific CD4+ T cells as determined by cell proliferation and IFN-gamma release.
1016 10477566 In particular, S. gordonii dose-dependently up-regulated expression of membrane molecules (MHC I and II, CD80, CD86, CD54, CD40, CD83) and reduced both phagocytic and endocytic activities.
1017 10477566 Furthermore, bacteria promoted in a dose-dependent manner DC release of cytokines (IL-6, TNF-alpha, IL-1beta, IL-12, TGF-beta, and IL-10) and of the chemokines IL-8, RANTES, IFN-gamma-inducible protein-10, and monokine induced by IFN-gamma.
1018 10486153 They expressed a set of DC-associated markers, such as MHC class II, CD1a, CD4, CD11a, CD40, CD58, CD80, CD83, CD86, and CXCR4.
1019 10490996 The apparent induction of a Th1 differentiation pathway was accompanied by the proliferation of MHC-independent NK cells and MHC-dependent CD8+ T cells.
1020 10491010 Tumor escape from CTL surveillance, through down regulation of individual tumor Ags and MHC alleles, might be overcome by polytope vaccines, which simultaneously target multiple cancer Ags.
1021 10496899 Gamma interferon (IFN-gamma)-secreting CD4+ T cells have long been established as an essential component of the protective immune response against Mycobacterium tuberculosis.
1022 10496899 It is now becoming evident from studies with the murine model of tuberculosis that an important role also exists for major histocompatibility complex (MHC) class I-restricted CD8+ T cells.
1023 10496899 Using FACScan analysis, we have shown that restimulation with live M. bovis BCG induced more CD8+-T-cell activation than the soluble antigen purified protein derivative and that these cells are actively producing the type 1 cytokines IFN-gamma and tumor necrosis factor alpha (TNF-alpha).
1024 10496899 The use of metabolic inhibitors and blocking antibodies revealed that the CD8+ T cells recognize antigen processed and presented via the classical MHC class I pathway.
1025 10496899 Gamma interferon (IFN-gamma)-secreting CD4+ T cells have long been established as an essential component of the protective immune response against Mycobacterium tuberculosis.
1026 10496899 It is now becoming evident from studies with the murine model of tuberculosis that an important role also exists for major histocompatibility complex (MHC) class I-restricted CD8+ T cells.
1027 10496899 Using FACScan analysis, we have shown that restimulation with live M. bovis BCG induced more CD8+-T-cell activation than the soluble antigen purified protein derivative and that these cells are actively producing the type 1 cytokines IFN-gamma and tumor necrosis factor alpha (TNF-alpha).
1028 10496899 The use of metabolic inhibitors and blocking antibodies revealed that the CD8+ T cells recognize antigen processed and presented via the classical MHC class I pathway.
1029 10501848 However, encounter of CD4(+) T cells with either MHC class II-expressing melanoma cells or certain tumor antigen-presenting APC has been reported to induce antigen-specific tolerance.
1030 10501850 Alternatively, MHC loss may render tumour cells susceptible to natural killer cell-mediated lysis because they are known to act as ligands for killer inhibitory receptors (KIRs).
1031 10518571 Identification of naturally processed and HLA-presented Epstein-Barr virus peptides recognized by CD4(+) or CD8(+) T lymphocytes from human blood.
1032 10518571 In a model system, we have evaluated the capacity of natural Epstein-Barr virus (EBV)-transformed B-lymphoblastoid cell line-extracted peptides to activate "memory" viral-specific CD4(+) or CD8(+) T cells freshly isolated from the blood of an EBV-seropositive individual using the IFN-gamma enzyme-linked immunospot assay.
1033 10518571 After HPLC fractionation and loading onto autologous dendritic cells, multiple naturally processed HLA class I and II-associated lymphoblastoid cell line-derived peptides were isolated that were capable of inducing IFN-gamma spot production by "memory" T lymphocytes.
1034 10519409 Modified vaccinia virus Ankara for delivery of human tyrosinase as melanoma-associated antigen: induction of tyrosinase- and melanoma-specific human leukocyte antigen A*0201-restricted cytotoxic T cells in vitro and in vivo.
1035 10519409 Tyrosinase-specific human CTLs were activated in vitro by MVA-hTyr-infected, HLA-A*0201-positive human dendritic cells.
1036 10519409 Importantly, an efficient tyrosinase- and melanoma-specific CTL response was induced in vitro using MVA-hTyr-infected autologous dendritic cells as activators for peripheral blood mononuclear cells derived from HLA-A*0201-positive melanoma patients despite prior vaccination against smallpox.
1037 10519409 Immunization of HLA-A*0201/Kb transgenic mice with MVA-hTyr induced A*0201-restricted CTLs specific for the human tyrosinase-derived peptide epitope 369-377.
1038 10519409 Modified vaccinia virus Ankara for delivery of human tyrosinase as melanoma-associated antigen: induction of tyrosinase- and melanoma-specific human leukocyte antigen A*0201-restricted cytotoxic T cells in vitro and in vivo.
1039 10519409 Tyrosinase-specific human CTLs were activated in vitro by MVA-hTyr-infected, HLA-A*0201-positive human dendritic cells.
1040 10519409 Importantly, an efficient tyrosinase- and melanoma-specific CTL response was induced in vitro using MVA-hTyr-infected autologous dendritic cells as activators for peripheral blood mononuclear cells derived from HLA-A*0201-positive melanoma patients despite prior vaccination against smallpox.
1041 10519409 Immunization of HLA-A*0201/Kb transgenic mice with MVA-hTyr induced A*0201-restricted CTLs specific for the human tyrosinase-derived peptide epitope 369-377.
1042 10519409 Modified vaccinia virus Ankara for delivery of human tyrosinase as melanoma-associated antigen: induction of tyrosinase- and melanoma-specific human leukocyte antigen A*0201-restricted cytotoxic T cells in vitro and in vivo.
1043 10519409 Tyrosinase-specific human CTLs were activated in vitro by MVA-hTyr-infected, HLA-A*0201-positive human dendritic cells.
1044 10519409 Importantly, an efficient tyrosinase- and melanoma-specific CTL response was induced in vitro using MVA-hTyr-infected autologous dendritic cells as activators for peripheral blood mononuclear cells derived from HLA-A*0201-positive melanoma patients despite prior vaccination against smallpox.
1045 10519409 Immunization of HLA-A*0201/Kb transgenic mice with MVA-hTyr induced A*0201-restricted CTLs specific for the human tyrosinase-derived peptide epitope 369-377.
1046 10520178 Human CD1 molecules, expressed on the surface of professional antigen-presenting cells (including dendritic cells, Langerhans' cells, B cells and activated monocytes) are structurally homologous to major histocompatibility complex (MHC) class I and class II molecules.
1047 10520178 CD1b and CD1c have been shown to present nonpeptide bacterial antigens to T cells.
1048 10520178 Human peripheral blood mononuclear cells (PBMC) were exposed to two medically important proteins, tetanus toxoid (TT) and purified protein derivative (PPD), with and without murine monoclonal antibodies (MoAbs) specific for CD1a, CD1b and CD1c.
1049 10520178 Simultaneous interaction of CD1 and MHC class II molecules was even more inhibitory to these antigen-specific proliferative responses.
1050 10520178 Human CD1 molecules, expressed on the surface of professional antigen-presenting cells (including dendritic cells, Langerhans' cells, B cells and activated monocytes) are structurally homologous to major histocompatibility complex (MHC) class I and class II molecules.
1051 10520178 CD1b and CD1c have been shown to present nonpeptide bacterial antigens to T cells.
1052 10520178 Human peripheral blood mononuclear cells (PBMC) were exposed to two medically important proteins, tetanus toxoid (TT) and purified protein derivative (PPD), with and without murine monoclonal antibodies (MoAbs) specific for CD1a, CD1b and CD1c.
1053 10520178 Simultaneous interaction of CD1 and MHC class II molecules was even more inhibitory to these antigen-specific proliferative responses.
1054 10525444 Iscoms prominently enhance the antigen targeting, uptake, and activity of antigen presenting cells including dendritic and B cells and macrophages resulting in the production of proinflammatory cytokines, above all interleukin (IL)-1, IL-6, and IL-12.
1055 10525444 The expression of costimulatory molecules major histocompatibility complex (MHC) class II, B7.1 and B7.2, is also enhanced.
1056 10525444 Iscoms enhance the Th1 type of response with increased production of IL-2 and interferon gamma.
1057 10525444 IL-4, IL-2, and interferon gamma (IFNgamma) together with the beta chemokines MIP-1alpha and MIP-1beta correlated with protection against challenge infection with a chimeric virus (simian immunodeficiency virus-human immunodeficiency virus).
1058 10558996 Persistence of memory CD8 T cells in MHC class I-deficient mice.
1059 10558996 Thus, after naïve CD8 T cells differentiate into memory cells, they evolve an MHC class I-independent "life-style" and do not require further stimulation with specific or cross-reactive antigen for their maintenance.
1060 10558996 Persistence of memory CD8 T cells in MHC class I-deficient mice.
1061 10558996 Thus, after naïve CD8 T cells differentiate into memory cells, they evolve an MHC class I-independent "life-style" and do not require further stimulation with specific or cross-reactive antigen for their maintenance.
1062 10566144 CD4+ T cells play a central role in orchestrating the host immune response against cancer, infectious diseases and autoimmune diseases, and we thus have attempted to identify major histocompatibility complex (MHC) class II-restricted tumor antigens as well.
1063 10569202 Because CD4+ T cells play a central role in orchestrating the host immune response against cancer, infectious diseases, and autoimmune diseases, a novel genetic approach has recently been developed to identify these MHC class II restricted tumor antigens.
1064 10569753 Isotype switching to immunoglobulin G (IgG) was abrogated in mice deficient in major histocompatibility complex (MHC) class II antigen (Ag)-T-cell receptor (TCR), B7-CD28, or CD40-CD40L interactions.
1065 10590071 In contrast, AML cells genetically modified to express IL-12 (IL12-AML) using murine stem cell virus (MSCV) p40 + p35 elicit very potent antileukemic activity.
1066 10590071 In vivo depletion of IL-12, interferon-gamma (IFN-gamma), or CD8(+) T cells after injections with live IL12-AML cells abrogates completely the antileukemia immune responses.
1067 10590071 Studies on the in vitro effects of IFN-gamma on AML cells demonstrate enhanced expression of major histocompatibility complex (MHC) and accessory molecules and induction of the costimulatory molecules B7.1 and B7.2, but no significant direct antiproliferative effect. (51)Cr release assays show that rejection of live IL12-AML cells supports the development of long-lasting leukemia-specific cytotoxic T lymphocyte (CTL) activity.
1068 10593490 Characterization of SIV-specific CD4+ T-helper proliferative responses in macaques immunized with live-attenuated SIV.
1069 10593490 SIV-specific proliferative responses were mediated by CD4+ T cells and were major histocompatibility (MHC) class II restricted.
1070 10593490 Intracellular flow-cytometric analysis demonstrated the production of interleukin (IL)-2, interferon (IFN)-gamma, RANTES and macrophage inhibitory protein-1alpha (MIP-1alpha) by T lymphocytes from SIVmac239deltanef-vaccinated animals following SIV p55 stimulation.
1071 10602887 Absence of the Ii protein, which normally blocks the antigenic-peptide-binding site of MHC class II molecules at synthesis in the endoplasmic reticulum, presumably increases the range of cancer-related epitopes presented to CD4+ helper T cells.
1072 10602887 The SaI murine sarcoma, which is MHC-class-I+ and MHC-class-II-, Ii-protein-, upon transfection with genes for either interferon gamma or the MHC class II transactivator, came to express MHC class II molecules and Ii protein.
1073 10602887 Absence of the Ii protein, which normally blocks the antigenic-peptide-binding site of MHC class II molecules at synthesis in the endoplasmic reticulum, presumably increases the range of cancer-related epitopes presented to CD4+ helper T cells.
1074 10602887 The SaI murine sarcoma, which is MHC-class-I+ and MHC-class-II-, Ii-protein-, upon transfection with genes for either interferon gamma or the MHC class II transactivator, came to express MHC class II molecules and Ii protein.
1075 10603392 The association of HLA-B53 with resistance to severe malaria in West Africa provided evidence that HLA class I-restricted CD8(+) T-cell responses play a role in protective immunity in African children, supporting data from rodent models of malaria.
1076 10604998 An early pseudorabies virus protein down-regulates porcine MHC class I expression by inhibition of transporter associated with antigen processing (TAP).
1077 10605047 Serial FNA of the same lesions were performed in five HLA-A*0201 patients vaccinated with the emulsified melanoma Ag (MA) epitopes: MART-1:27-35; tyrosinase:368-376(370D); gp100:280-288(288V); and gp100:209-217 (210M).
1078 10606632 MHC class II tetramers identify peptide-specific human CD4(+) T cells proliferating in response to influenza A antigen.
1079 10606632 After 7 days of proliferation in response to stimulation by HA peptide or whole influenza vaccine, cells staining positive with the HA tetramer had undergone between 6 and 9 divisions and were CD3(+), CD4(+), CD25(+), and CD8(-), characteristic of activated T helper cells responding to antigen.
1080 10611973 Mechanisms of viral interference with MHC class I antigen processing and presentation.
1081 10614142 HCV Core, NS3 and NS4 proteins are the most immunogenic antigens for B cells and HLA class II-restricted CD4+ T cells.
1082 10614142 For its part, liver-infiltrating CD8+ CTL recognize epitopes within the Core, E1, E2/NS1 and NS2 proteins in a HLA class I restricted manner.
1083 10614142 CTL responses to HCV Core, NS3, NS4 and NS5 have been detected in peripheral blood of patients chronically infected with HCV.
1084 10649617 HIV-1 specific CD8+ MHC Class I restricted cytotoxic T-lymphocytes were not seen in a subset of participants tested at a single timepoint.
1085 10654199 TIL phenotypes studied here indicated CD3 80 +/- 21%, CD4 37 +/- 21%, CD8 44 +/- 18% and HLA DR 69 +/- 24% after IL2 induction, in contrast, to CD3 20 +/- 12%, CD4 10 +/- 7%, CD8 11 +/- 3% and HLA DR 30 +/- 16% before induction.
1086 10654199 The results of a tumor vaccine using TNF-alpha gene transduction demonstrated that the expression of HLA Class I and HLA Class II were dramatically increased 87% and 43%.
1087 10656428 Pre- and postvaccination peripheral blood mononuclear cells (PMBCs) of the eight patients positive for HLA-class I A2 allele, were incubated with the HLA-A2-CEA peptide CAP-1 and interleukin 2.
1088 10656428 Fluorescence-activated cell sorter analysis of the T-cell lines established from patients after ALVAC-CEA vaccination revealed that most were CD8+/CD4-, but many also had a CD8+/CD4+ component.
1089 10684264 Gag-specific cytotoxic T-lymphocyte (CTL) responses were detected in all MVA-gag-pol-immunized macaques by both functional assays and flow cytometric analyses of CD8(+) T cells that bound a specific MHC complex class I-peptide tetramer, with levels peaking after the second immunization.
1090 10687136 The significance of CD4+ lymphocytes and major histocompatibility complex (MHC) class II-restricted antigens in antitumor immunity has been demonstrated in several animal models as well as in some human tumors.
1091 10687136 The sarcoma cells expressing the MHC-peptide complex were rejected by immunocompetent BALB/c mice, and in vivo T-cell subset depletion experiments suggested the importance of CD4+ cells in the rejection.
1092 10687136 Such covalent MHC-peptide complexes could prove useful in studies on the role of CD4+ lymphocytes in antitumor immune responses, and also in designing new, more effective vaccine approaches to the immunotherapy of cancer, as class II-restricted tumor-associated antigens are identified for human cancers.
1093 10687136 The significance of CD4+ lymphocytes and major histocompatibility complex (MHC) class II-restricted antigens in antitumor immunity has been demonstrated in several animal models as well as in some human tumors.
1094 10687136 The sarcoma cells expressing the MHC-peptide complex were rejected by immunocompetent BALB/c mice, and in vivo T-cell subset depletion experiments suggested the importance of CD4+ cells in the rejection.
1095 10687136 Such covalent MHC-peptide complexes could prove useful in studies on the role of CD4+ lymphocytes in antitumor immune responses, and also in designing new, more effective vaccine approaches to the immunotherapy of cancer, as class II-restricted tumor-associated antigens are identified for human cancers.
1096 10687136 The significance of CD4+ lymphocytes and major histocompatibility complex (MHC) class II-restricted antigens in antitumor immunity has been demonstrated in several animal models as well as in some human tumors.
1097 10687136 The sarcoma cells expressing the MHC-peptide complex were rejected by immunocompetent BALB/c mice, and in vivo T-cell subset depletion experiments suggested the importance of CD4+ cells in the rejection.
1098 10687136 Such covalent MHC-peptide complexes could prove useful in studies on the role of CD4+ lymphocytes in antitumor immune responses, and also in designing new, more effective vaccine approaches to the immunotherapy of cancer, as class II-restricted tumor-associated antigens are identified for human cancers.
1099 10699581 Genetically-modified tumors expressing various cytokines, major histocompatibility complex (MHC) molecules, or costimulatory molecules such as B7-1 (CD80) or B7-2 (CD86) can induce tumor-specific immune responses.
1100 10706736 In vitro priming with adenovirus/gp100 antigen-transduced dendritic cells reveals the epitope specificity of HLA-A*0201-restricted CD8+ T cells in patients with melanoma.
1101 10706736 Replication-deficient recombinant adenovirus (Ad) encoding human gp100 or MART-1 melanoma Ag was used to transduce human dendritic cells (DC) ex vivo as a model system for cancer vaccine therapy.
1102 10706736 Thus, patients with metastatic melanoma are not tolerant to gp100 Ag based on the detection of CD8+ T cells specific for multiple HLA-A*0201-restricted, gp100-derived epitopes.
1103 10706736 In vitro priming with adenovirus/gp100 antigen-transduced dendritic cells reveals the epitope specificity of HLA-A*0201-restricted CD8+ T cells in patients with melanoma.
1104 10706736 Replication-deficient recombinant adenovirus (Ad) encoding human gp100 or MART-1 melanoma Ag was used to transduce human dendritic cells (DC) ex vivo as a model system for cancer vaccine therapy.
1105 10706736 Thus, patients with metastatic melanoma are not tolerant to gp100 Ag based on the detection of CD8+ T cells specific for multiple HLA-A*0201-restricted, gp100-derived epitopes.
1106 10706970 Definition of MHC-restricted CTL epitopes from non-variable number of tandem repeat sequence of MUC1.
1107 10706970 Using the whole native MUC1 molecule, the human milk fat globule membrane antigen (HMFG) linked to mannan, cytotoxic T cell precursors (CTLp) can be generated in BALB/c, C57BL/6, transgenic HLA-A*0201/K(b) and double transgenic HLA-A*0201/K(b)xhuman MUC1 (A2 K(b)MUC1) mice.
1108 10706970 Definition of MHC-restricted CTL epitopes from non-variable number of tandem repeat sequence of MUC1.
1109 10706970 Using the whole native MUC1 molecule, the human milk fat globule membrane antigen (HMFG) linked to mannan, cytotoxic T cell precursors (CTLp) can be generated in BALB/c, C57BL/6, transgenic HLA-A*0201/K(b) and double transgenic HLA-A*0201/K(b)xhuman MUC1 (A2 K(b)MUC1) mice.
1110 10712678 In wild-type mice, both CD4 and CD8 cell numbers increased in the gut following Salmonella challenge, together with increased expression of major histocompatibility complex (MHC) II and vascular cell adhesion molecule-1 (VCAM-1).
1111 10712678 Following oral challenge, antilipopolysaccharide (LPS) and antiphosphoryl choline antibodies increased by more than 100-fold in both serum and faecal pellet extracts of IFNgamma-/- mice compared with wild-type mice.
1112 10713345 Dietary lutein also increased the percentages of CD4+ and CD21+ lymphocytes on Week 12 but had no significant effect on pan T, CD8 and MHC class II markers.
1113 10741724 To explore the possibility that wild-type sequence p53 peptides could also be used in vaccines for patients expressing HLA-A24 antigen, another frequent HLA class I allele, we investigated the induction of HLA-A24-restricted p53-specific CTLs from the peripheral blood lymphocytes of normal donors.
1114 10741724 Of six p53-derived peptides possessing an HLA-A24 binding motif, the p53 peptide 125-134 (p53(125-134)) was found to have a high binding capacity and induced peptide-specific CTLs from peripheral blood mononuclear cells, using peptide-pulsed autologous dendritic cells and subsequent cultivation with cytokines interleukin 2 and interleukin 7.
1115 10746554 Phase 2 trial of vaccination with tyrosinase peptides and granulocyte-macrophage colony-stimulating factor in patients with metastatic melanoma.
1116 10746554 This phase II study was performed to determine the induction of a specific T-cell response, the clinical response rate, and toxicity of vaccination with different HLA class I-binding peptide epitopes derived from the melanocyte differentiation antigen tyrosinase in patients with stage IV melanoma.
1117 10746554 Patients received intradermal injections of 200 microgram [corrected] peptide corresponding to their HLA type on day 3, and 75 or 150 microg granulocyte-macrophage colony-stimulating factor on days 1 to 4.
1118 10746554 This study shows limited clinical and immunologic activity of HLA class 1-peptide vaccination in combination with granulocyte-macrophage colony-stimulating factor in stage IV melanoma patients.
1119 10752474 Melanoma-reactive HLA-A x 0201-restricted cytotoxic T lymphocyte (CTL) lines generated in vitro lyse autologous and HLA-matched allogeneic melanoma cells and recognize multiple shared peptide antigens from tyrosinase, MART-1, and Pme117/gp100.
1120 10752474 All four are deficient in expression of the melanocytic differentiation proteins (MDP) tyrosinase, Pme117/gp100, gp75/ trp-1, and MART-1/Melan-A.
1121 10766024 At this time, much attention is focused on using peptides to be presented by MHC class I molecules to both induce and be targets for CD8+ cytolytic T cells.
1122 10770624 To explore the feasibility of designing vaccination protocols in acute leukemia patients with cytokine gene-transduced leukemic cells, we studied in vitro the growth potential of human leukemic cells transduced with the interleukin-2 (IL-2), IL-7, or IL-7 plus IL-2 genes, as well as the capacity of generating both autologous and allogeneic cytotoxic lymphocytes directed against the parental cells.
1123 10770624 A lymphoblastic T-cell line, ST4, obtained from a patient in long-lasting complete remission, was retrovirally engineered with the IL-2, IL-7, and IL-7 plus IL-2 genes; in addition, clones releasing different amounts of the cytokines were obtained by limiting dilution.
1124 10770624 On the contrary, when IL-7- or IL-7-IL-2-producing cells were used as stimulators, only a delay in leukemic cell overgrowth was observed, and lymphocytes were completely cleared from the cultures after day 60.
1125 10770624 IL-7 production by the different clones ranged between 11 and 36 ng/mL/10(6) cells/72 hours, whereas the highest IL-2-producing IL-7-IL-2 clone released 50 IU/mL/10(6) cells/72 hours of IL-2.
1126 10770624 Autologous and allogeneic long-term MLTCs (up to 35 days) with ST4/IL-2#A7 as the stimulator were capable of generating cytotoxic effectors equally endowed with both major histocompatibility complex (MHC) class I-unrestricted and -restricted activity against parental ST4 cells.
1127 10770624 By day 18 of both autologous and allogeneic cultures, a substantial proportion of CD56+ cells was consistently recorded; this was coupled to a predominantly MHC-unrestricted cytotoxic activity directed against parental ST4 cells.
1128 10770624 The results of this study demonstrate that IL-2 gene-transduced human acute leukemia cells cocultured with both autologous and allogeneic lymphocytes are capable of inducing a strong MHC-unrestricted anti-leukemic activity and subsequently "educating" MHC class I-restricted anti-leukemic effectors.
1129 10770624 To explore the feasibility of designing vaccination protocols in acute leukemia patients with cytokine gene-transduced leukemic cells, we studied in vitro the growth potential of human leukemic cells transduced with the interleukin-2 (IL-2), IL-7, or IL-7 plus IL-2 genes, as well as the capacity of generating both autologous and allogeneic cytotoxic lymphocytes directed against the parental cells.
1130 10770624 A lymphoblastic T-cell line, ST4, obtained from a patient in long-lasting complete remission, was retrovirally engineered with the IL-2, IL-7, and IL-7 plus IL-2 genes; in addition, clones releasing different amounts of the cytokines were obtained by limiting dilution.
1131 10770624 On the contrary, when IL-7- or IL-7-IL-2-producing cells were used as stimulators, only a delay in leukemic cell overgrowth was observed, and lymphocytes were completely cleared from the cultures after day 60.
1132 10770624 IL-7 production by the different clones ranged between 11 and 36 ng/mL/10(6) cells/72 hours, whereas the highest IL-2-producing IL-7-IL-2 clone released 50 IU/mL/10(6) cells/72 hours of IL-2.
1133 10770624 Autologous and allogeneic long-term MLTCs (up to 35 days) with ST4/IL-2#A7 as the stimulator were capable of generating cytotoxic effectors equally endowed with both major histocompatibility complex (MHC) class I-unrestricted and -restricted activity against parental ST4 cells.
1134 10770624 By day 18 of both autologous and allogeneic cultures, a substantial proportion of CD56+ cells was consistently recorded; this was coupled to a predominantly MHC-unrestricted cytotoxic activity directed against parental ST4 cells.
1135 10770624 The results of this study demonstrate that IL-2 gene-transduced human acute leukemia cells cocultured with both autologous and allogeneic lymphocytes are capable of inducing a strong MHC-unrestricted anti-leukemic activity and subsequently "educating" MHC class I-restricted anti-leukemic effectors.
1136 10770624 To explore the feasibility of designing vaccination protocols in acute leukemia patients with cytokine gene-transduced leukemic cells, we studied in vitro the growth potential of human leukemic cells transduced with the interleukin-2 (IL-2), IL-7, or IL-7 plus IL-2 genes, as well as the capacity of generating both autologous and allogeneic cytotoxic lymphocytes directed against the parental cells.
1137 10770624 A lymphoblastic T-cell line, ST4, obtained from a patient in long-lasting complete remission, was retrovirally engineered with the IL-2, IL-7, and IL-7 plus IL-2 genes; in addition, clones releasing different amounts of the cytokines were obtained by limiting dilution.
1138 10770624 On the contrary, when IL-7- or IL-7-IL-2-producing cells were used as stimulators, only a delay in leukemic cell overgrowth was observed, and lymphocytes were completely cleared from the cultures after day 60.
1139 10770624 IL-7 production by the different clones ranged between 11 and 36 ng/mL/10(6) cells/72 hours, whereas the highest IL-2-producing IL-7-IL-2 clone released 50 IU/mL/10(6) cells/72 hours of IL-2.
1140 10770624 Autologous and allogeneic long-term MLTCs (up to 35 days) with ST4/IL-2#A7 as the stimulator were capable of generating cytotoxic effectors equally endowed with both major histocompatibility complex (MHC) class I-unrestricted and -restricted activity against parental ST4 cells.
1141 10770624 By day 18 of both autologous and allogeneic cultures, a substantial proportion of CD56+ cells was consistently recorded; this was coupled to a predominantly MHC-unrestricted cytotoxic activity directed against parental ST4 cells.
1142 10770624 The results of this study demonstrate that IL-2 gene-transduced human acute leukemia cells cocultured with both autologous and allogeneic lymphocytes are capable of inducing a strong MHC-unrestricted anti-leukemic activity and subsequently "educating" MHC class I-restricted anti-leukemic effectors.
1143 10779556 We demonstrated that peripheral T cell tolerance toward murine melanoma self-antigens gp100 and TRP-2 can be broken by an autologous oral DNA vaccine containing the murine ubiquitin gene fused to minigenes encoding peptide epitopes gp100(25-33) and TRP-2(181-188).
1144 10779556 These epitopes contain dominant anchor residues for MHC class I antigen alleles H-2D(b) and H-2K(b), respectively.
1145 10779556 Tumor-protective immunity was mediated by MHC class I antigen-restricted CD8(+) T cells that secreted T(H)1 cytokine IFN-gamma and induced tumor rejection and growth suppression after a lethal challenge with B16G3. 26 murine melanoma cells.
1146 10779556 We demonstrated that peripheral T cell tolerance toward murine melanoma self-antigens gp100 and TRP-2 can be broken by an autologous oral DNA vaccine containing the murine ubiquitin gene fused to minigenes encoding peptide epitopes gp100(25-33) and TRP-2(181-188).
1147 10779556 These epitopes contain dominant anchor residues for MHC class I antigen alleles H-2D(b) and H-2K(b), respectively.
1148 10779556 Tumor-protective immunity was mediated by MHC class I antigen-restricted CD8(+) T cells that secreted T(H)1 cytokine IFN-gamma and induced tumor rejection and growth suppression after a lethal challenge with B16G3. 26 murine melanoma cells.
1149 10782864 Immunotherapy with vaccines combining MHC class II/CD80+ tumor cells with interleukin-12 reduces established metastatic disease and stimulates immune effectors and monokine induced by interferon gamma.
1150 10782864 Two such mouse models are used in this report to demonstrate the therapeutic efficacy and to probe the mechanisms of a novel combination immunotherapy consisting of the cytokine interleukin-12 (IL-12) combined with a previously described vaccine based on MHC class II, CD80-expressing cells.
1151 10782864 C57BL/6 mice with 7-day established intravenous B16 melF10 lung metastases show a similar response following immunotherapy with IL-12 plus a vaccine based on B16 MHC class II, CD80-expressing cells.
1152 10782864 In both systems the combination therapy of cells plus IL-12 is more effective than IL-12 or the cellular vaccine alone, although, in the 4T1 system, optimal activity does not require MHC class II and CD80 expression in the vaccine cells.
1153 10782864 The cell-based vaccines were originally designed to activate tumor-specific CD4+ T lymphocytes specifically and thereby provide helper activity to tumor-cytotoxic CD8+ T cells, and IL-12 was added to the therapy to facilitate T helper type 1 lymphocyte (Th1) differentiation.
1154 10782864 In vivo depletion experiments for CD4+ and CD8+ T cells and natural killer (NK) cells and tumor challenge experiments in beige/nude/XID immunodeficient mice demonstrate that the therapeutic effect is not exclusively dependent on a single cell population, suggesting that T and NK cells are acting together to optimize the response.
1155 10782864 IL-12 may also be enhancing the immunotherapy via induction of the chemokine Mig (monokine induced by interferon gamma), because reverse PCR experiments demonstrate that Mig is present in the lungs of mice receiving therapy and is most likely synthesized by the tumor cells.
1156 10786687 Genetic immunization with a single injection of dendritic cells (DCs) expressing a model melanoma antigen generates antigen-specific, MHC-restricted, protective immune responses.
1157 10786687 In conclusion, C3H mice but not C57BL/6 mice receiving multiple vaccinations with DCs expressing the MART-1 tumor antigen show decreased protection associated with deviation from a type 1 to a type 2 cytokine response attributable to a Fas-receptor mediated clearance of antigen-specific IFN-gamma-producing cells.
1158 10802297 Dietary lutein increased (P<0.05) lymphocyte proliferative response to all three mitogens and increased the percentages of cells expressing CD5, CD4, CD8 and major histocompatibility complex class II (MHC II) molecules.
1159 10820384 T cell activation assays revealed that the observed type III-mediated antigen translocation led to a p60 peptide-specific MHC class I-restricted antigen presentation.
1160 10823832 In order to better investigate structure-stability relationships, we have determined by circular dichroism spectroscopy the thermal stability of a class I MHC protein, HLA-B*2705, in complex with a set of 39 singly substituted peptide analogues.
1161 10825145 Here, we test in this postsurgical model, a novel cell-based vaccine, combining MHC class II, CD80(B7.1), and SEB superantigen.
1162 10825145 These therapeutic effects are particularly noteworthy because: (a) the postoperative model demonstrates that early metastases responsible for morbidity are established by 2 weeks after tumor inoculation with 7 x 10(3) parental 4T1 cells into the mammary gland; (b) the immunotherapy is started 4 weeks after tumor inoculation when the mice contain extensive, pre-established, disseminated metastases; and (c) CD4+ and CD8+ T cells are required for the effect.
1163 10854153 The rationale for this strategy is that T-cells need two signals before they can mount a cytotoxic response: the binding of the T-cell receptor (TCR) to an antigenic peptide presented on major histocompatibility complex (MHC) molecules and the binding of CD28 to B7-1.
1164 10856797 Because of the resistance of cancer patients to immunization, ex vivo immunization of macrophage/dendritic cells was examined using oxidized mannan MUC1 to target the mannose receptor and the MHC Class I antigen presentation pathway.
1165 10858206 MHC restriction analysis demonstrated that individual T-cell lines specifically recognized the complete Ag85B either in association with one of the self HLA-DRB1, DRB3, or DRB4 gene products or nonspecifically in a promiscuous manner.
1166 10861037 Transgenic expression of a fusion protein of hen egg lysozyme and an encephalitogenic peptide of myelin basic protein (MBP) residues 84-105, coexpressed with MHC class II, causes profound tolerance to hen egg lysozyme, while maintaining a near normal response to MBP.
1167 10869775 Mice immunised with human epithelial mucin MUC1 coupled to oxidised mannan produce MUC1 specific MHC Class 1 restricted CD8(+) cytotoxic T cells and are completely protected from the development of MUC1(+) tumours; such therapy may be applicable to humans.
1168 10873071 Induction of CEA-specific T-cell precursors was assessed by an ELISPOT assay looking for the production of IFN-gamma.
1169 10873071 After four vaccinations, patients who were HLA-A-2-positive demonstrated increases in their CEA-specific T-cell precursor frequencies to a CEA-A2-binding peptide from baseline.
1170 10878367 Recently, we have described Mtb-specific CD8+ T cells that are neither HLA-A-, B-, or C- nor group 1 CD1-restricted.
1171 10878367 An IFN-gamma enzyme-linked immunospot assay was used to determine the frequency of Mtb-reactive CD8+ T cells directly from PBMC.
1172 10878392 Previously, we identified and established the antigenicity of 17 CD8+ T cell epitopes from five P. falciparum Ags that are restricted by multiple common HLA class I alleles.
1173 10885560 At least five independent mechanisms leading to changes in HLA expression were seen: HLA class I allelic transcription but no protein; abnormal HLA class I allelic transcription; no HLA-B locus transcription; loss of heterozygosity (LOH); no gammaIFN-mediated upregulation of HLA class I expression, and/or no interferon-gamma (gammaIFN)-mediated HLA class II induction.
1174 10897045 Evaluation of CD8(+) T-cell frequencies by the Elispot assay in healthy individuals and in patients with metastatic melanoma immunized with tyrosinase peptide.
1175 10897045 CD8(+) T-cell reactivity was determined with an interferon (IFN)-gamma Elispot assay detecting T cells at the single cell level that secrete IFN-gamma.
1176 10897045 Healthy HLA-A*0201-positive individuals showed a similar mean frequency of CD8(+) cells recognizing a tyrosinase peptide, YMDGTMSQV, when compared with melanoma patients prior to immunization.
1177 10897045 The frequencies of CD8(+) cells recognizing the tyrosinase peptide remained relatively constant over time in healthy individuals.
1178 10897045 Nine HLA-A*0201-positive patients with stage IV metastatic melanoma were immunized intradermally with the tyrosinase peptide together with the immune adjuvant QS-21 in a peptide dose escalation study with 3 patients per dose group.
1179 10897045 Two patients demonstrated a significant increase in the frequency of CD8(+) cells recognizing the tyrosinase peptide during the course of immunization, from approx. 1/16,000 CD8(+) T cells to approx. 1/4,000 in the first patient and from approx. 1/14,000 to approx. 1/2,000 in the second patient.
1180 10897045 Evaluation of CD8(+) T-cell frequencies by the Elispot assay in healthy individuals and in patients with metastatic melanoma immunized with tyrosinase peptide.
1181 10897045 CD8(+) T-cell reactivity was determined with an interferon (IFN)-gamma Elispot assay detecting T cells at the single cell level that secrete IFN-gamma.
1182 10897045 Healthy HLA-A*0201-positive individuals showed a similar mean frequency of CD8(+) cells recognizing a tyrosinase peptide, YMDGTMSQV, when compared with melanoma patients prior to immunization.
1183 10897045 The frequencies of CD8(+) cells recognizing the tyrosinase peptide remained relatively constant over time in healthy individuals.
1184 10897045 Nine HLA-A*0201-positive patients with stage IV metastatic melanoma were immunized intradermally with the tyrosinase peptide together with the immune adjuvant QS-21 in a peptide dose escalation study with 3 patients per dose group.
1185 10897045 Two patients demonstrated a significant increase in the frequency of CD8(+) cells recognizing the tyrosinase peptide during the course of immunization, from approx. 1/16,000 CD8(+) T cells to approx. 1/4,000 in the first patient and from approx. 1/14,000 to approx. 1/2,000 in the second patient.
1186 10915855 They were subsequently surface-stained for CD8 and for intracellular interferon gamma (IFN-gamma) and analyzed by flow cytometry.
1187 10915855 The specificity and sensitivity of this assay, staining of antigen-activated lymphocytes (SAAL), was comparable to that of surface staining with major histocompatibily class (MHC) I-peptide tetramers or of staining of peptide re-stimulated CD8(+) T cells for intracellular IFN-gamma.
1188 10916759 Phase 1 study in patients with metastatic melanoma of immunization with dendritic cells presenting epitopes derived from the melanoma-associated antigens MART-1 and gp100.
1189 10916759 Furthermore, DC-like function can be elicited from peripheral blood monocytes cultured in vitro with interleukin-4 and granulocyte-macrophage colony-stimulating factor.
1190 10916759 The DCs were generated by 5- to 7-day incubation in interleukin-4 (1,000 U/mL) and granulocyte-macrophage colony-stimulating factor (1,000 U/mL) of peripheral blood monocytes obtained by leukapheresis.
1191 10916759 Before administration, the DCs were pulsed separately with the HLA-A*0201-associated melanoma epitopes MART-1(27-35) and gp-100-209-2M.
1192 10917901 Compared with unsupplemented dogs, those fed 20 or 50 mg of beta-carotene had higher CD4+ cell numbers and CD4:CD8 ratio.
1193 10917901 However, there was no treatment difference in CD8+, CD21+ and major histocompatability complex (MHC) class II+ cells.
1194 10918477 Ad infection (MOI 200) of BMDC induced significant increases in IL 12 p40 protein in culture supernatants (6 x that of uninfected BMDC and similar to that observed with addition of LPS and CD40 crosslinking antibody).
1195 10918477 Consistent with DC activation, FACs analysis showed BMDC infected with Ad vectors up-regulated the surface expression of B7-2, ICAM-1 and MHC II.
1196 10918477 Additional experiments evaluated the role of virus attachment, internalization and gene expression using IL-12 p40 production as a marker of DC activation.
1197 10918477 Neither heat-inactivated Ad nor peptides containing the RGD sequence (the primary component of Ad penton base which interacts with cell surface integrins) induced significant amounts of IL12 p40.
1198 10918477 In contrast, psoralen/UV-inactivated Ad showed similar levels of IL12 p40 production compared with intact Ad.
1199 10928070 Immunization with TGF-beta antisense oligonucleotide-modified autologous tumor vaccine enhances the antitumor immunity of MBT-2 tumor-bearing mice through upregulation of MHC class I and Fas expressions.
1200 10928070 The result of flow cytometry analysis reveals that decreased production of TGF-beta led to the increased expressions of MHC class I molecule and Fas on the surface of MBT-2 tumor cells.
1201 10928070 Our result implies that decreasing the amount of TGF-beta secreted from the autologous tumor vaccine by antisense strategy may significantly improve its immunogenicity through up-regulation of both MHC class I and Fas expressions.
1202 10928070 Immunization with TGF-beta antisense oligonucleotide-modified autologous tumor vaccine enhances the antitumor immunity of MBT-2 tumor-bearing mice through upregulation of MHC class I and Fas expressions.
1203 10928070 The result of flow cytometry analysis reveals that decreased production of TGF-beta led to the increased expressions of MHC class I molecule and Fas on the surface of MBT-2 tumor cells.
1204 10928070 Our result implies that decreasing the amount of TGF-beta secreted from the autologous tumor vaccine by antisense strategy may significantly improve its immunogenicity through up-regulation of both MHC class I and Fas expressions.
1205 10928070 Immunization with TGF-beta antisense oligonucleotide-modified autologous tumor vaccine enhances the antitumor immunity of MBT-2 tumor-bearing mice through upregulation of MHC class I and Fas expressions.
1206 10928070 The result of flow cytometry analysis reveals that decreased production of TGF-beta led to the increased expressions of MHC class I molecule and Fas on the surface of MBT-2 tumor cells.
1207 10928070 Our result implies that decreasing the amount of TGF-beta secreted from the autologous tumor vaccine by antisense strategy may significantly improve its immunogenicity through up-regulation of both MHC class I and Fas expressions.
1208 10930667 Mice immunised with oxidised mannan-MUC1 fusion protein (M-FP) develop MHC restricted CD8(+) cytotoxic T cells.
1209 10931134 In vivo studies using mice with targeted mutations in CD8 or MHC class II or depleted of CD8 or CD4 lymphocyte subsets demonstrate that tumour regression following therapeutic hspE7 immunization is CD8-dependent and CD4-independent.
1210 10941827 We recently have reported that Wilms' tumor gene WT1 is highly expressed not only in leukemias but also in various types of solid tumors and that WT1 protein is a novel tumor antigen against which cytotoxic T lymphocytes (CTLs) can be elicited by immunization with 9-mer WT1 peptides capable of binding to major histocompatibility complex (MHC) class I molecules.
1211 10941827 The mice vaccinated with the WT1 plasmid DNA elicited CTLs against the WT1 protein, and the CTLs specifically killed WT1-expressing tumor cells in a MHC class I-restricted manner.
1212 10941827 We recently have reported that Wilms' tumor gene WT1 is highly expressed not only in leukemias but also in various types of solid tumors and that WT1 protein is a novel tumor antigen against which cytotoxic T lymphocytes (CTLs) can be elicited by immunization with 9-mer WT1 peptides capable of binding to major histocompatibility complex (MHC) class I molecules.
1213 10941827 The mice vaccinated with the WT1 plasmid DNA elicited CTLs against the WT1 protein, and the CTLs specifically killed WT1-expressing tumor cells in a MHC class I-restricted manner.
1214 10942395 C57/BL6 (B6) mice were injected with synthetic peptides from the natural sequence of WT1 containing motifs for binding to major histocompatibility (MHC) class II molecules.
1215 10942395 Immunization with MHC class I binding peptides induced WT1 peptide-specific cytotoxic T-lymphocyte (CTL) that specifically lysed TRAMP-C and BLKSV40.
1216 10942395 C57/BL6 (B6) mice were injected with synthetic peptides from the natural sequence of WT1 containing motifs for binding to major histocompatibility (MHC) class II molecules.
1217 10942395 Immunization with MHC class I binding peptides induced WT1 peptide-specific cytotoxic T-lymphocyte (CTL) that specifically lysed TRAMP-C and BLKSV40.
1218 10946264 The secondary CD8+IFN-gamma+ DbNP366-specific response was much greater in parental H2b than in H2kxbF1 mice, but the sizes of the CD8+ sets specific for KkNP50 and DbNP366 were essentially equivalent in the F1 animals.
1219 10946264 A further, MHC-related effect was also identified for the KkNS1152 epitope, which was consistently associated with a greater CD8+IFN-gamma+ response in H2KkDb recombinant than in (H2KkDk x H2KbDb)F1 mice.
1220 10950153 CD8+ CTL clones specific for these peptides were established and they lysed HER2+ tumor cells in a human leukocyte antigen (HLA)-A24-restricted manner.
1221 10950153 To elicit specific CD8+ T cell immune responses against cancer, the development of efficient devices to deliver tumor antigen peptides to the major histocompatibility complex (MHC) class I pathway constitutes a central issue.
1222 10950153 We have developed a novel formula of hydrophobized polysaccharide nanoparticles which can deliver a HER2 oncoprotein containing an epitope peptide to the MHC class I pathway.
1223 10950153 These complexes were able to induce CD8+ CTLs against HER2+ tumors.
1224 10950153 CTLs were MHC class I restricted and specifically recognized HER2p63-71, a part of a truncated HER2 protein used as an immunogen.
1225 10950153 CD8+ CTL clones specific for these peptides were established and they lysed HER2+ tumor cells in a human leukocyte antigen (HLA)-A24-restricted manner.
1226 10950153 To elicit specific CD8+ T cell immune responses against cancer, the development of efficient devices to deliver tumor antigen peptides to the major histocompatibility complex (MHC) class I pathway constitutes a central issue.
1227 10950153 We have developed a novel formula of hydrophobized polysaccharide nanoparticles which can deliver a HER2 oncoprotein containing an epitope peptide to the MHC class I pathway.
1228 10950153 These complexes were able to induce CD8+ CTLs against HER2+ tumors.
1229 10950153 CTLs were MHC class I restricted and specifically recognized HER2p63-71, a part of a truncated HER2 protein used as an immunogen.
1230 10950153 CD8+ CTL clones specific for these peptides were established and they lysed HER2+ tumor cells in a human leukocyte antigen (HLA)-A24-restricted manner.
1231 10950153 To elicit specific CD8+ T cell immune responses against cancer, the development of efficient devices to deliver tumor antigen peptides to the major histocompatibility complex (MHC) class I pathway constitutes a central issue.
1232 10950153 We have developed a novel formula of hydrophobized polysaccharide nanoparticles which can deliver a HER2 oncoprotein containing an epitope peptide to the MHC class I pathway.
1233 10950153 These complexes were able to induce CD8+ CTLs against HER2+ tumors.
1234 10950153 CTLs were MHC class I restricted and specifically recognized HER2p63-71, a part of a truncated HER2 protein used as an immunogen.
1235 10954578 A tetrameric recombinant major histocompatibility complex (MHC) class II-peptide complex was used to quantitate human immunodeficiency virus type 1 (HIV-1) envelope (Env)-specific CD4(+) T cells in vaccinated and in simian/human immunodeficiency virus (SHIV)-infected rhesus monkeys.
1236 11005833 Direct enumeration of Borrelia-reactive CD4 T cells ex vivo by using MHC class II tetramers.
1237 11005833 We characterized antigen-specific CD4(+) T cells in six patients with treatment-resistant Lyme arthritis, using an HLA-DRB1*0401 major histocompatibility complex (MHC) class II tetramer covalently loaded with OspA(164-175), an immunodominant epitope of Borrelia burgdorferi.
1238 11005833 Direct analysis of OspA-tetramer binding CD4(+) cells in patients expressing the HLA-DRB1*0401 allele revealed frequencies of between <0.005 and 0.1% in peripheral blood (n = 6), and between <0.005 and 3.1% in synovial fluid (n = 3).
1239 11005833 OspA-tetramer(+)CD4(+) cells were directly cloned at 1 cell per well and expanded by mitogen and IL-2 on allogeneic feeder cells.
1240 11005833 Clones generated from peripheral blood revealed a different pattern of responsiveness when compared with clones generated from synovial fluid, as measured by proliferation, IFN-gamma, and IL-13 secretion.
1241 11005833 Direct enumeration of Borrelia-reactive CD4 T cells ex vivo by using MHC class II tetramers.
1242 11005833 We characterized antigen-specific CD4(+) T cells in six patients with treatment-resistant Lyme arthritis, using an HLA-DRB1*0401 major histocompatibility complex (MHC) class II tetramer covalently loaded with OspA(164-175), an immunodominant epitope of Borrelia burgdorferi.
1243 11005833 Direct analysis of OspA-tetramer binding CD4(+) cells in patients expressing the HLA-DRB1*0401 allele revealed frequencies of between <0.005 and 0.1% in peripheral blood (n = 6), and between <0.005 and 3.1% in synovial fluid (n = 3).
1244 11005833 OspA-tetramer(+)CD4(+) cells were directly cloned at 1 cell per well and expanded by mitogen and IL-2 on allogeneic feeder cells.
1245 11005833 Clones generated from peripheral blood revealed a different pattern of responsiveness when compared with clones generated from synovial fluid, as measured by proliferation, IFN-gamma, and IL-13 secretion.
1246 11012624 We examined 59 clinical isolates and five laboratory clones of P. falciparum for polymorphism in the N- and C-terminal regions of LSA-1, evaluated binding of the corresponding peptides to selected HLA class I alleles, and measured IFN-gamma responses in residents of a malaria-endemic area of Papua New Guinea where HLA-A*1101, -24, -B13, and -B40 are the most common class I alleles.
1247 11012756 An immunodominant epitope of human immunodeficiency virus-1 (HIV-1) gp160 recognized by Dd class I major histocompatibility complex (MHC) molecule-restricted, CD8+ cytotoxic T lymphocytes (CTL) was originally identified as a peptide composed of 15 amino acids (P18IIIB: RIQRGPGRAFVTIGK).
1248 11012763 We found no significant differences in the up-regulation of major histocompatibility complex (MHC) class II antigens in the epithelium, up-regulation of vascular cell adhesion molecule-1 (VCAM-1) in vascular endothelium, or recruitment of T cells to the mucosa, indicating that the memory T-cell response to virus challenge was the same in intact and B-cell KO mice.
1249 11012976 HLA-A*0201 restricted CD8+ T-lymphocyte responses to malaria: identification of new Plasmodium falciparum epitopes by IFN-gamma ELISPOT.
1250 11012976 Using a combination of short-term cell culture and IFN-gamma ELISPOT, we studied CD8+ T-lymphocyte responses to a panel of HLA-A*0201 binding peptides.
1251 11012976 We conclude that the modified IFN-gamma ELISPOT assay is a sensitive technique to monitor antigen-specific CD8+ T-lymphocyte responses in human malaria which may help in the improvement and assessment of the efficacy of malaria subunit vaccines.
1252 11012976 HLA-A*0201 restricted CD8+ T-lymphocyte responses to malaria: identification of new Plasmodium falciparum epitopes by IFN-gamma ELISPOT.
1253 11012976 Using a combination of short-term cell culture and IFN-gamma ELISPOT, we studied CD8+ T-lymphocyte responses to a panel of HLA-A*0201 binding peptides.
1254 11012976 We conclude that the modified IFN-gamma ELISPOT assay is a sensitive technique to monitor antigen-specific CD8+ T-lymphocyte responses in human malaria which may help in the improvement and assessment of the efficacy of malaria subunit vaccines.
1255 11016652 Defining promiscuous MHC class II helper T-cell epitopes for the HER2/neu tumor antigen.
1256 11016652 Nevertheless, it is expected that inclusion of peptide epitopes capable of eliciting HER2/neu-specific T helper responses into these vaccines may enhance their effectiveness in the clinic.
1257 11035120 The animal model used was Human Human D(b) (HHD) mice, which are deficient for mouse MHC class I molecules (beta(2)-microglobulin(-/-) D(b-/-)) and transgenic for a chimeric HLA-A*0201/D(b) molecule covalently bound to the human beta(2)-microglobulin (HHD(+/+)).
1258 11035120 Moreover, genetic immunization of HLA-A2 transgenic mice generates IFN-gamma-secreting CD8(+) T lymphocytes specific for endogenously processed peptides and with recognition specificities similar to those described during self-limited infection in humans.
1259 11035735 CD4+ alpha beta T cells and gamma interferon (IFN-gamma) are centrally implicated in the primary immunoprotective response.
1260 11035735 We find that a full-strength primary response depends on beta(2)-microglobulin (class I major histocompatibility complex [MHC] and class II MHC and on IFN-gamma and interleukin-6 (IL-6) but not on TAP1, perforin, IL-4, Fas ligand, or inducible nitric oxide synthetase.
1261 11035735 Indeed, MHC class II-deficient and IFN-gamma-deficient mice are as susceptible to primary infection as mice deficient in all alpha beta T cells.
1262 11035735 Strikingly, the requirements for a highly effective alpha beta-T-cell-driven memory response are less stringent, requiring neither IFN-gamma nor IL-6 nor class I MHC.
1263 11035735 CD4+ alpha beta T cells and gamma interferon (IFN-gamma) are centrally implicated in the primary immunoprotective response.
1264 11035735 We find that a full-strength primary response depends on beta(2)-microglobulin (class I major histocompatibility complex [MHC] and class II MHC and on IFN-gamma and interleukin-6 (IL-6) but not on TAP1, perforin, IL-4, Fas ligand, or inducible nitric oxide synthetase.
1265 11035735 Indeed, MHC class II-deficient and IFN-gamma-deficient mice are as susceptible to primary infection as mice deficient in all alpha beta T cells.
1266 11035735 Strikingly, the requirements for a highly effective alpha beta-T-cell-driven memory response are less stringent, requiring neither IFN-gamma nor IL-6 nor class I MHC.
1267 11035735 CD4+ alpha beta T cells and gamma interferon (IFN-gamma) are centrally implicated in the primary immunoprotective response.
1268 11035735 We find that a full-strength primary response depends on beta(2)-microglobulin (class I major histocompatibility complex [MHC] and class II MHC and on IFN-gamma and interleukin-6 (IL-6) but not on TAP1, perforin, IL-4, Fas ligand, or inducible nitric oxide synthetase.
1269 11035735 Indeed, MHC class II-deficient and IFN-gamma-deficient mice are as susceptible to primary infection as mice deficient in all alpha beta T cells.
1270 11035735 Strikingly, the requirements for a highly effective alpha beta-T-cell-driven memory response are less stringent, requiring neither IFN-gamma nor IL-6 nor class I MHC.
1271 11086086 Identification of major epitopes of Mycobacterium tuberculosis AG85B that are recognized by HLA-A*0201-restricted CD8+ T cells in HLA-transgenic mice and humans.
1272 11086086 Although several nonprotein ligands have been identified for CD1-restricted CD8(+) CTLs, epitopes for classical MHC class I-restricted CD8(+) T cells, which most likely represent a majority among CD8(+) T cells, have remained ill defined.
1273 11086086 In this study, we demonstrate the presence of HLA class I-restricted, CD8(+) T cells against Ag85B of M. tuberculosis in HLA-A2/K(b) transgenic mice and HLA-A*0201(+) humans.
1274 11086086 Moreover, two immunodominant Ag85 peptide epitopes for HLA-A*0201-restricted, M. tuberculosis-reactive CD8(+) CTLs were identified.
1275 11086086 These CD8(+) T cells produced IFN-gamma and TNF-alpha and recognized Ag-pulsed or bacillus Calmette-Guérin-infected, HLA-A*0201-positive, but not HLA-A*0201-negative or uninfected human macrophages.
1276 11086086 Using fluorescent peptide/HLA-A*0201 tetramers, Ag85-specific CD8(+) T cells could be visualized in bacillus Calmette-Guérin-responsive, HLA-A*0201(+) individuals.
1277 11086086 Collectively, our results demonstrate the presence of HLA class I-restricted CD8(+) CTL against a major Ag of M. tuberculosis and identify Ag85B epitopes that are strongly recognized by HLA-A*0201-restricted CD8(+) T cells in humans and mice.
1278 11086086 Identification of major epitopes of Mycobacterium tuberculosis AG85B that are recognized by HLA-A*0201-restricted CD8+ T cells in HLA-transgenic mice and humans.
1279 11086086 Although several nonprotein ligands have been identified for CD1-restricted CD8(+) CTLs, epitopes for classical MHC class I-restricted CD8(+) T cells, which most likely represent a majority among CD8(+) T cells, have remained ill defined.
1280 11086086 In this study, we demonstrate the presence of HLA class I-restricted, CD8(+) T cells against Ag85B of M. tuberculosis in HLA-A2/K(b) transgenic mice and HLA-A*0201(+) humans.
1281 11086086 Moreover, two immunodominant Ag85 peptide epitopes for HLA-A*0201-restricted, M. tuberculosis-reactive CD8(+) CTLs were identified.
1282 11086086 These CD8(+) T cells produced IFN-gamma and TNF-alpha and recognized Ag-pulsed or bacillus Calmette-Guérin-infected, HLA-A*0201-positive, but not HLA-A*0201-negative or uninfected human macrophages.
1283 11086086 Using fluorescent peptide/HLA-A*0201 tetramers, Ag85-specific CD8(+) T cells could be visualized in bacillus Calmette-Guérin-responsive, HLA-A*0201(+) individuals.
1284 11086086 Collectively, our results demonstrate the presence of HLA class I-restricted CD8(+) CTL against a major Ag of M. tuberculosis and identify Ag85B epitopes that are strongly recognized by HLA-A*0201-restricted CD8(+) T cells in humans and mice.
1285 11086086 Identification of major epitopes of Mycobacterium tuberculosis AG85B that are recognized by HLA-A*0201-restricted CD8+ T cells in HLA-transgenic mice and humans.
1286 11086086 Although several nonprotein ligands have been identified for CD1-restricted CD8(+) CTLs, epitopes for classical MHC class I-restricted CD8(+) T cells, which most likely represent a majority among CD8(+) T cells, have remained ill defined.
1287 11086086 In this study, we demonstrate the presence of HLA class I-restricted, CD8(+) T cells against Ag85B of M. tuberculosis in HLA-A2/K(b) transgenic mice and HLA-A*0201(+) humans.
1288 11086086 Moreover, two immunodominant Ag85 peptide epitopes for HLA-A*0201-restricted, M. tuberculosis-reactive CD8(+) CTLs were identified.
1289 11086086 These CD8(+) T cells produced IFN-gamma and TNF-alpha and recognized Ag-pulsed or bacillus Calmette-Guérin-infected, HLA-A*0201-positive, but not HLA-A*0201-negative or uninfected human macrophages.
1290 11086086 Using fluorescent peptide/HLA-A*0201 tetramers, Ag85-specific CD8(+) T cells could be visualized in bacillus Calmette-Guérin-responsive, HLA-A*0201(+) individuals.
1291 11086086 Collectively, our results demonstrate the presence of HLA class I-restricted CD8(+) CTL against a major Ag of M. tuberculosis and identify Ag85B epitopes that are strongly recognized by HLA-A*0201-restricted CD8(+) T cells in humans and mice.
1292 11086086 Identification of major epitopes of Mycobacterium tuberculosis AG85B that are recognized by HLA-A*0201-restricted CD8+ T cells in HLA-transgenic mice and humans.
1293 11086086 Although several nonprotein ligands have been identified for CD1-restricted CD8(+) CTLs, epitopes for classical MHC class I-restricted CD8(+) T cells, which most likely represent a majority among CD8(+) T cells, have remained ill defined.
1294 11086086 In this study, we demonstrate the presence of HLA class I-restricted, CD8(+) T cells against Ag85B of M. tuberculosis in HLA-A2/K(b) transgenic mice and HLA-A*0201(+) humans.
1295 11086086 Moreover, two immunodominant Ag85 peptide epitopes for HLA-A*0201-restricted, M. tuberculosis-reactive CD8(+) CTLs were identified.
1296 11086086 These CD8(+) T cells produced IFN-gamma and TNF-alpha and recognized Ag-pulsed or bacillus Calmette-Guérin-infected, HLA-A*0201-positive, but not HLA-A*0201-negative or uninfected human macrophages.
1297 11086086 Using fluorescent peptide/HLA-A*0201 tetramers, Ag85-specific CD8(+) T cells could be visualized in bacillus Calmette-Guérin-responsive, HLA-A*0201(+) individuals.
1298 11086086 Collectively, our results demonstrate the presence of HLA class I-restricted CD8(+) CTL against a major Ag of M. tuberculosis and identify Ag85B epitopes that are strongly recognized by HLA-A*0201-restricted CD8(+) T cells in humans and mice.
1299 11086086 Identification of major epitopes of Mycobacterium tuberculosis AG85B that are recognized by HLA-A*0201-restricted CD8+ T cells in HLA-transgenic mice and humans.
1300 11086086 Although several nonprotein ligands have been identified for CD1-restricted CD8(+) CTLs, epitopes for classical MHC class I-restricted CD8(+) T cells, which most likely represent a majority among CD8(+) T cells, have remained ill defined.
1301 11086086 In this study, we demonstrate the presence of HLA class I-restricted, CD8(+) T cells against Ag85B of M. tuberculosis in HLA-A2/K(b) transgenic mice and HLA-A*0201(+) humans.
1302 11086086 Moreover, two immunodominant Ag85 peptide epitopes for HLA-A*0201-restricted, M. tuberculosis-reactive CD8(+) CTLs were identified.
1303 11086086 These CD8(+) T cells produced IFN-gamma and TNF-alpha and recognized Ag-pulsed or bacillus Calmette-Guérin-infected, HLA-A*0201-positive, but not HLA-A*0201-negative or uninfected human macrophages.
1304 11086086 Using fluorescent peptide/HLA-A*0201 tetramers, Ag85-specific CD8(+) T cells could be visualized in bacillus Calmette-Guérin-responsive, HLA-A*0201(+) individuals.
1305 11086086 Collectively, our results demonstrate the presence of HLA class I-restricted CD8(+) CTL against a major Ag of M. tuberculosis and identify Ag85B epitopes that are strongly recognized by HLA-A*0201-restricted CD8(+) T cells in humans and mice.
1306 11086086 Identification of major epitopes of Mycobacterium tuberculosis AG85B that are recognized by HLA-A*0201-restricted CD8+ T cells in HLA-transgenic mice and humans.
1307 11086086 Although several nonprotein ligands have been identified for CD1-restricted CD8(+) CTLs, epitopes for classical MHC class I-restricted CD8(+) T cells, which most likely represent a majority among CD8(+) T cells, have remained ill defined.
1308 11086086 In this study, we demonstrate the presence of HLA class I-restricted, CD8(+) T cells against Ag85B of M. tuberculosis in HLA-A2/K(b) transgenic mice and HLA-A*0201(+) humans.
1309 11086086 Moreover, two immunodominant Ag85 peptide epitopes for HLA-A*0201-restricted, M. tuberculosis-reactive CD8(+) CTLs were identified.
1310 11086086 These CD8(+) T cells produced IFN-gamma and TNF-alpha and recognized Ag-pulsed or bacillus Calmette-Guérin-infected, HLA-A*0201-positive, but not HLA-A*0201-negative or uninfected human macrophages.
1311 11086086 Using fluorescent peptide/HLA-A*0201 tetramers, Ag85-specific CD8(+) T cells could be visualized in bacillus Calmette-Guérin-responsive, HLA-A*0201(+) individuals.
1312 11086086 Collectively, our results demonstrate the presence of HLA class I-restricted CD8(+) CTL against a major Ag of M. tuberculosis and identify Ag85B epitopes that are strongly recognized by HLA-A*0201-restricted CD8(+) T cells in humans and mice.
1313 11086086 Identification of major epitopes of Mycobacterium tuberculosis AG85B that are recognized by HLA-A*0201-restricted CD8+ T cells in HLA-transgenic mice and humans.
1314 11086086 Although several nonprotein ligands have been identified for CD1-restricted CD8(+) CTLs, epitopes for classical MHC class I-restricted CD8(+) T cells, which most likely represent a majority among CD8(+) T cells, have remained ill defined.
1315 11086086 In this study, we demonstrate the presence of HLA class I-restricted, CD8(+) T cells against Ag85B of M. tuberculosis in HLA-A2/K(b) transgenic mice and HLA-A*0201(+) humans.
1316 11086086 Moreover, two immunodominant Ag85 peptide epitopes for HLA-A*0201-restricted, M. tuberculosis-reactive CD8(+) CTLs were identified.
1317 11086086 These CD8(+) T cells produced IFN-gamma and TNF-alpha and recognized Ag-pulsed or bacillus Calmette-Guérin-infected, HLA-A*0201-positive, but not HLA-A*0201-negative or uninfected human macrophages.
1318 11086086 Using fluorescent peptide/HLA-A*0201 tetramers, Ag85-specific CD8(+) T cells could be visualized in bacillus Calmette-Guérin-responsive, HLA-A*0201(+) individuals.
1319 11086086 Collectively, our results demonstrate the presence of HLA class I-restricted CD8(+) CTL against a major Ag of M. tuberculosis and identify Ag85B epitopes that are strongly recognized by HLA-A*0201-restricted CD8(+) T cells in humans and mice.
1320 11093141 CD8(+) T lymphocytes, which are major immune effectors, require primary stimulation by dendritic cells (DC) presenting MHC class I molecule-bound epitopes.
1321 11093141 This internalization induced functional stimulation of specific CD8(+) T lymphocytes in IFN-gamma ELISPOT assays.
1322 11101805 Soluble extracellular protein antigens are notoriously poor stimulators of CD8+ cytotoxic T-lymphocyte (CTL) responses, largely because these antigens have inefficient access to an endogenous cytosolic pathway of the major histocompatibility complex (MHC) class I-dependent antigen presentation.
1323 11106934 Selection and characterization of MUC1-specific CD8+ T cells from MUC1 transgenic mice immunized with dendritic-carcinoma fusion cells.
1324 11106934 Here we demonstrate that lymph node cells from MUC1.Tg mice immunized with the FC/MUC1 fusion cells proliferate in response to MUC1 antigen by a mechanism dependent on the function of CD4, major histocompatibility complex (MHC) class II, B7-1, B7-2, CD28, CD40 and CD40 ligand.
1325 11106934 The findings demonstrate that stimulation of lymph node cells with MUC1 results in selection of MUC1-specific CD8+ T cells.
1326 11106934 We show that the CD8+ T cells exhibit MUC1-specific cytotoxic T lymphocyte (CTL) activity by recognition of MUC1 peptides presented in the context of MHC class I molecules Kb and Db.
1327 11106934 The MUC1-specific CD8+ T cells also exhibit antitumour activity against MUC1-positive metastases, but with no apparent reactivity against normal tissues.
1328 11106934 These results indicate that immunization of MUC1.Tg mice with FC/MUC1 reverses immunological unresponsiveness to MUC1 by presentation of MUC1 peptides in the presence of costimulatory signals and generates MHC-restricted MUC1-specific CD8+ T cells.
1329 11106934 Selection and characterization of MUC1-specific CD8+ T cells from MUC1 transgenic mice immunized with dendritic-carcinoma fusion cells.
1330 11106934 Here we demonstrate that lymph node cells from MUC1.Tg mice immunized with the FC/MUC1 fusion cells proliferate in response to MUC1 antigen by a mechanism dependent on the function of CD4, major histocompatibility complex (MHC) class II, B7-1, B7-2, CD28, CD40 and CD40 ligand.
1331 11106934 The findings demonstrate that stimulation of lymph node cells with MUC1 results in selection of MUC1-specific CD8+ T cells.
1332 11106934 We show that the CD8+ T cells exhibit MUC1-specific cytotoxic T lymphocyte (CTL) activity by recognition of MUC1 peptides presented in the context of MHC class I molecules Kb and Db.
1333 11106934 The MUC1-specific CD8+ T cells also exhibit antitumour activity against MUC1-positive metastases, but with no apparent reactivity against normal tissues.
1334 11106934 These results indicate that immunization of MUC1.Tg mice with FC/MUC1 reverses immunological unresponsiveness to MUC1 by presentation of MUC1 peptides in the presence of costimulatory signals and generates MHC-restricted MUC1-specific CD8+ T cells.
1335 11106934 Selection and characterization of MUC1-specific CD8+ T cells from MUC1 transgenic mice immunized with dendritic-carcinoma fusion cells.
1336 11106934 Here we demonstrate that lymph node cells from MUC1.Tg mice immunized with the FC/MUC1 fusion cells proliferate in response to MUC1 antigen by a mechanism dependent on the function of CD4, major histocompatibility complex (MHC) class II, B7-1, B7-2, CD28, CD40 and CD40 ligand.
1337 11106934 The findings demonstrate that stimulation of lymph node cells with MUC1 results in selection of MUC1-specific CD8+ T cells.
1338 11106934 We show that the CD8+ T cells exhibit MUC1-specific cytotoxic T lymphocyte (CTL) activity by recognition of MUC1 peptides presented in the context of MHC class I molecules Kb and Db.
1339 11106934 The MUC1-specific CD8+ T cells also exhibit antitumour activity against MUC1-positive metastases, but with no apparent reactivity against normal tissues.
1340 11106934 These results indicate that immunization of MUC1.Tg mice with FC/MUC1 reverses immunological unresponsiveness to MUC1 by presentation of MUC1 peptides in the presence of costimulatory signals and generates MHC-restricted MUC1-specific CD8+ T cells.
1341 11115698 HBV-specific antibody and both CD4+ and CD8+ T cell responses were measured before and after each immunization.
1342 11115698 In volunteers who were positive for the HLA class I A2 allele, the vaccine also induced antigen-specific CD8+ T cells that bound HLA-A2/HBsAg(335-343) tetramers, secreted IFN-gamma, and lysed target cells presenting a hepatitis B surface antigen (HBsAg) CTL epitope.
1343 11119299 We, therefore, considered whether it is possible to assemble a panel of HLA-A and/or HLA-B alleles that would allow the formulation of a single vaccine for a set of Caucasian, Black, or Asian populations.
1344 11119299 Our findings suggest that HLA-A alleles may be preferred targets because of the increased heterogeneity at HLA-B, although addition of a single HLA-B allele to a set of HLA-A alleles improved coverage.
1345 11119299 We, therefore, considered whether it is possible to assemble a panel of HLA-A and/or HLA-B alleles that would allow the formulation of a single vaccine for a set of Caucasian, Black, or Asian populations.
1346 11119299 Our findings suggest that HLA-A alleles may be preferred targets because of the increased heterogeneity at HLA-B, although addition of a single HLA-B allele to a set of HLA-A alleles improved coverage.
1347 11120838 A highly sensitive enzyme-linked immunospot (ELISPOT) assay for single cell IFN-gamma release was used to screen CD8(+) T cells with overlapping peptides spanning the mycobacterial major secreted protein, Ag85A.
1348 11120838 Three peptides consistently induced a high frequency of IFN-gamma responsive CD8(+) T cells, and two HLA-A*0201 binding motifs, P(48-56) and P(242-250), were revealed within the core sequences.
1349 11120838 CD8(+) T cells responding to the 9-mer epitopes were visualized within fresh blood by ELISPOT using free peptide or by binding of HLA-A*0201 tetrameric complexes.
1350 11120838 Tetramer assays revealed a 6-fold higher frequency of peptide-specific T cells than IFN-gamma ELISPOT assays, indicating functional heterogeneity within the CD8(+) T cell population.
1351 11120838 These results demonstrate a previously unrecognized, MHC class I-restricted, CD8(+) CTL response to a major secreted Ag of mycobacteria and supports the use of Ag85A as a candidate vaccine against tuberculosis.
1352 11120838 A highly sensitive enzyme-linked immunospot (ELISPOT) assay for single cell IFN-gamma release was used to screen CD8(+) T cells with overlapping peptides spanning the mycobacterial major secreted protein, Ag85A.
1353 11120838 Three peptides consistently induced a high frequency of IFN-gamma responsive CD8(+) T cells, and two HLA-A*0201 binding motifs, P(48-56) and P(242-250), were revealed within the core sequences.
1354 11120838 CD8(+) T cells responding to the 9-mer epitopes were visualized within fresh blood by ELISPOT using free peptide or by binding of HLA-A*0201 tetrameric complexes.
1355 11120838 Tetramer assays revealed a 6-fold higher frequency of peptide-specific T cells than IFN-gamma ELISPOT assays, indicating functional heterogeneity within the CD8(+) T cell population.
1356 11120838 These results demonstrate a previously unrecognized, MHC class I-restricted, CD8(+) CTL response to a major secreted Ag of mycobacteria and supports the use of Ag85A as a candidate vaccine against tuberculosis.
1357 11120838 A highly sensitive enzyme-linked immunospot (ELISPOT) assay for single cell IFN-gamma release was used to screen CD8(+) T cells with overlapping peptides spanning the mycobacterial major secreted protein, Ag85A.
1358 11120838 Three peptides consistently induced a high frequency of IFN-gamma responsive CD8(+) T cells, and two HLA-A*0201 binding motifs, P(48-56) and P(242-250), were revealed within the core sequences.
1359 11120838 CD8(+) T cells responding to the 9-mer epitopes were visualized within fresh blood by ELISPOT using free peptide or by binding of HLA-A*0201 tetrameric complexes.
1360 11120838 Tetramer assays revealed a 6-fold higher frequency of peptide-specific T cells than IFN-gamma ELISPOT assays, indicating functional heterogeneity within the CD8(+) T cell population.
1361 11120838 These results demonstrate a previously unrecognized, MHC class I-restricted, CD8(+) CTL response to a major secreted Ag of mycobacteria and supports the use of Ag85A as a candidate vaccine against tuberculosis.
1362 11120863 Direct detection and magnetic isolation of Chlamydia trachomatis major outer membrane protein-specific CD8+ CTLs with HLA class I tetramers.
1363 11120863 This study provides conclusive evidence of in vivo induction of HLA class I-restricted CD8(+) CTL responses to C. trachomatis MOMP.
1364 11120863 Direct detection and magnetic isolation of Chlamydia trachomatis major outer membrane protein-specific CD8+ CTLs with HLA class I tetramers.
1365 11120863 This study provides conclusive evidence of in vivo induction of HLA class I-restricted CD8(+) CTL responses to C. trachomatis MOMP.
1366 11122456 Polymophonuclear cells (PMN) of healthy donors do not express major histocompatibility complex (MHC) class II antigens or the T-cell costimulatory molecules CD80 or CD86.
1367 11122456 We now report that, by culturing PMN of healthy donors with autologous serum, interferon-gamma (IFN-gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF), de novo synthesis of MHC class II, CD80 and CD86 could be induced.
1368 11122456 MHC class II-positive PMN acquired the capacity to present staphylococcus enterotoxin to peripheral T cells, apparent as induction of interleukin-2 (IL-2) synthesis and proliferation of the T cells.
1369 11122456 Polymophonuclear cells (PMN) of healthy donors do not express major histocompatibility complex (MHC) class II antigens or the T-cell costimulatory molecules CD80 or CD86.
1370 11122456 We now report that, by culturing PMN of healthy donors with autologous serum, interferon-gamma (IFN-gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF), de novo synthesis of MHC class II, CD80 and CD86 could be induced.
1371 11122456 MHC class II-positive PMN acquired the capacity to present staphylococcus enterotoxin to peripheral T cells, apparent as induction of interleukin-2 (IL-2) synthesis and proliferation of the T cells.
1372 11122456 Polymophonuclear cells (PMN) of healthy donors do not express major histocompatibility complex (MHC) class II antigens or the T-cell costimulatory molecules CD80 or CD86.
1373 11122456 We now report that, by culturing PMN of healthy donors with autologous serum, interferon-gamma (IFN-gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF), de novo synthesis of MHC class II, CD80 and CD86 could be induced.
1374 11122456 MHC class II-positive PMN acquired the capacity to present staphylococcus enterotoxin to peripheral T cells, apparent as induction of interleukin-2 (IL-2) synthesis and proliferation of the T cells.
1375 11123429 Synergistic suppressive effect of double transfection of tumor necrosis factor-alpha and interleukin 12 genes on tumorigenicity of Meth-A cells.
1376 11123429 Tumor necrosis factor-alpha (TNF-alpha) and interleukin 12 (IL-12), both potent antitumor cytokines, are known to be involved in the host's antitumor immune surveillance in tumor bearers, via different mechanisms.
1377 11123429 Thus, double transfection of TNF-alpha and IL-12 genes was considered to bring about synergistic suppressive effects on the tumorigenicity of transfectants through the activation of killer cells by produced cytokines and the enhancement of expression of MHC class I, II and B7.1 molecules.
1378 11134287 To test this concept in a relevant disease model we sought to identify multiple simian immunodeficiency virus (SIV)-derived CD8(+) epitopes bound by a single nonhuman primate major histocompatibility complex (MHC) class I molecule.
1379 11134287 We had previously identified the peptide binding motif of Mamu-A*01(2), a common rhesus macaque MHC class I molecule that presents the immunodominant SIV gag-derived cytotoxic T lymphocyte (CTL) epitope Gag_CM9 (CTPYDINQM).
1380 11134287 To test this concept in a relevant disease model we sought to identify multiple simian immunodeficiency virus (SIV)-derived CD8(+) epitopes bound by a single nonhuman primate major histocompatibility complex (MHC) class I molecule.
1381 11134287 We had previously identified the peptide binding motif of Mamu-A*01(2), a common rhesus macaque MHC class I molecule that presents the immunodominant SIV gag-derived cytotoxic T lymphocyte (CTL) epitope Gag_CM9 (CTPYDINQM).
1382 11159003 Like infectious viruses, conditioned medium from RSV-infected cells (RSV-CM) induces naive cells to coordinately express a gene cluster encoding the transporter associated with antigen presentation 1 (TAP1) and low molecular mass protein (LMP) 2 and LMP7.
1383 11159003 Neutralization of RSV-CM with antibodies to interferon (IFN)-beta largely blocked TAP1/LMP2/LMP7 expression, whereas anti-interleukin-1 antibodies were without effect, and recombinant IFN-beta increased TAP1/LMP2/LMP7 expression to levels produced by RSV-CM.
1384 11159003 LMP2, LMP7, and TAP1 expression were required for MHC class I upregulation because the irreversible proteasome inhibitor lactacystin or transfection with a competitive TAP1 inhibitor blocked inducible class I expression.
1385 11159003 We conclude that RSV infection coordinately increases MHC class I expression and proteasome activity through the paracrine action of IFN-beta to induce expression of the TAP1/LMP2/LMP7 locus, an event that may be important in the initiation of CTL-mediated lung injury.
1386 11159003 Like infectious viruses, conditioned medium from RSV-infected cells (RSV-CM) induces naive cells to coordinately express a gene cluster encoding the transporter associated with antigen presentation 1 (TAP1) and low molecular mass protein (LMP) 2 and LMP7.
1387 11159003 Neutralization of RSV-CM with antibodies to interferon (IFN)-beta largely blocked TAP1/LMP2/LMP7 expression, whereas anti-interleukin-1 antibodies were without effect, and recombinant IFN-beta increased TAP1/LMP2/LMP7 expression to levels produced by RSV-CM.
1388 11159003 LMP2, LMP7, and TAP1 expression were required for MHC class I upregulation because the irreversible proteasome inhibitor lactacystin or transfection with a competitive TAP1 inhibitor blocked inducible class I expression.
1389 11159003 We conclude that RSV infection coordinately increases MHC class I expression and proteasome activity through the paracrine action of IFN-beta to induce expression of the TAP1/LMP2/LMP7 locus, an event that may be important in the initiation of CTL-mediated lung injury.
1390 11160013 Thus, flow cytometry analyses showed an increase in the expression of major histocompatibility complex (MHC) class II, CD40, CD54, CD58, CD83, and CD86 molecules on the monocytes.
1391 11160013 The increase in cell surface expression of MHC class II did not occur in the presence of neutralizing IL-4 antibody or in cultures of highly purified monocytes or CD4-depleted mononuclear cells.
1392 11160013 Activated Th2 cells release IL-4, which in turn can induce an increase in the expression of MHC class II molecules on monocytes.
1393 11160013 Thus, flow cytometry analyses showed an increase in the expression of major histocompatibility complex (MHC) class II, CD40, CD54, CD58, CD83, and CD86 molecules on the monocytes.
1394 11160013 The increase in cell surface expression of MHC class II did not occur in the presence of neutralizing IL-4 antibody or in cultures of highly purified monocytes or CD4-depleted mononuclear cells.
1395 11160013 Activated Th2 cells release IL-4, which in turn can induce an increase in the expression of MHC class II molecules on monocytes.
1396 11160013 Thus, flow cytometry analyses showed an increase in the expression of major histocompatibility complex (MHC) class II, CD40, CD54, CD58, CD83, and CD86 molecules on the monocytes.
1397 11160013 The increase in cell surface expression of MHC class II did not occur in the presence of neutralizing IL-4 antibody or in cultures of highly purified monocytes or CD4-depleted mononuclear cells.
1398 11160013 Activated Th2 cells release IL-4, which in turn can induce an increase in the expression of MHC class II molecules on monocytes.
1399 11163665 The success of this approach depends on the ability to direct the CTL epitopes to the MHC class I antigen presentation pathway.
1400 11169964 Identification of three non-VNTR MUC1-derived HLA-A*0201-restricted T-cell epitopes that induce protective anti-tumor immunity in HLA-A2/K(b)-transgenic mice.
1401 11169964 We have identified several MUC1-derived peptides mapping outside the variable number tandem repeat region that comply with the peptide-binding motif for HLA-A*0201 and that become processed into stable major histocompatibility complex-peptide complexes as assessed by in vitro assays.
1402 11169964 Identification of three non-VNTR MUC1-derived HLA-A*0201-restricted T-cell epitopes that induce protective anti-tumor immunity in HLA-A2/K(b)-transgenic mice.
1403 11169964 We have identified several MUC1-derived peptides mapping outside the variable number tandem repeat region that comply with the peptide-binding motif for HLA-A*0201 and that become processed into stable major histocompatibility complex-peptide complexes as assessed by in vitro assays.
1404 11181647 Immunization with a HER-2/neu helper peptide vaccine generates HER-2/neu CD8 T-cell immunity in cancer patients.
1405 11181647 CD4 T-cell help is required during the generation and maintenance of effective antitumor CD8 T cell-mediated immunity.
1406 11181647 The goal of this study was to determine whether HER-2/neu-specific CD8 T-cell immunity could be elicited using HER-2/neu-derived MHC class II "helper" peptides, which contain encompassed HLA-A2-binding motifs.
1407 11181647 These results demonstrate that HER-2/neu MHC class II epitopes containing encompassed MHC class I epitopes are able to induce long-lasting HER-2-specific IFN-gamma-producing CD8 T cells.
1408 11181647 Immunization with a HER-2/neu helper peptide vaccine generates HER-2/neu CD8 T-cell immunity in cancer patients.
1409 11181647 CD4 T-cell help is required during the generation and maintenance of effective antitumor CD8 T cell-mediated immunity.
1410 11181647 The goal of this study was to determine whether HER-2/neu-specific CD8 T-cell immunity could be elicited using HER-2/neu-derived MHC class II "helper" peptides, which contain encompassed HLA-A2-binding motifs.
1411 11181647 These results demonstrate that HER-2/neu MHC class II epitopes containing encompassed MHC class I epitopes are able to induce long-lasting HER-2-specific IFN-gamma-producing CD8 T cells.
1412 11182225 We identified 4 HLA-A, 7 HLA-B, and 5 HLA-C specificities that were observed at high frequencies in the Botswana population: A30, A02, A23, A68, B58, B72, B42, B8, B18, B44, B45, Cw7, Cw2, Cw17, Cw6, and Cw4.
1413 11196165 In this report, we show that HSP70 purified from human melanoma can activate T cells recognizing melanoma differentiation antigens in an antigen- and HLA class I-dependent fashion.
1414 11196165 HLA class I-restricted anti-melanoma T cells were susceptible to MHC-restricted, HSP70-dependent stimulation, indicating that HSP70 complexed peptides were able to gain access to the class I HLA presentation pathway.
1415 11196165 In addition, MHC matching between the melanoma cells used as a source of HSP and the responding T cells were not required, indicating that HSP70 activation may occur across MHC barriers.
1416 11196165 Besides the MHC-restricted and peptide-dependent activation pathway, HSP70 with no endogenous complexed peptides or HSP70 purified from antigen-negative cells was also able to induce IFN-gamma release by antimelanoma T cells by a MHC-independent mechanism.
1417 11196165 In this report, we show that HSP70 purified from human melanoma can activate T cells recognizing melanoma differentiation antigens in an antigen- and HLA class I-dependent fashion.
1418 11196165 HLA class I-restricted anti-melanoma T cells were susceptible to MHC-restricted, HSP70-dependent stimulation, indicating that HSP70 complexed peptides were able to gain access to the class I HLA presentation pathway.
1419 11196165 In addition, MHC matching between the melanoma cells used as a source of HSP and the responding T cells were not required, indicating that HSP70 activation may occur across MHC barriers.
1420 11196165 Besides the MHC-restricted and peptide-dependent activation pathway, HSP70 with no endogenous complexed peptides or HSP70 purified from antigen-negative cells was also able to induce IFN-gamma release by antimelanoma T cells by a MHC-independent mechanism.
1421 11196165 In this report, we show that HSP70 purified from human melanoma can activate T cells recognizing melanoma differentiation antigens in an antigen- and HLA class I-dependent fashion.
1422 11196165 HLA class I-restricted anti-melanoma T cells were susceptible to MHC-restricted, HSP70-dependent stimulation, indicating that HSP70 complexed peptides were able to gain access to the class I HLA presentation pathway.
1423 11196165 In addition, MHC matching between the melanoma cells used as a source of HSP and the responding T cells were not required, indicating that HSP70 activation may occur across MHC barriers.
1424 11196165 Besides the MHC-restricted and peptide-dependent activation pathway, HSP70 with no endogenous complexed peptides or HSP70 purified from antigen-negative cells was also able to induce IFN-gamma release by antimelanoma T cells by a MHC-independent mechanism.
1425 11196165 In this report, we show that HSP70 purified from human melanoma can activate T cells recognizing melanoma differentiation antigens in an antigen- and HLA class I-dependent fashion.
1426 11196165 HLA class I-restricted anti-melanoma T cells were susceptible to MHC-restricted, HSP70-dependent stimulation, indicating that HSP70 complexed peptides were able to gain access to the class I HLA presentation pathway.
1427 11196165 In addition, MHC matching between the melanoma cells used as a source of HSP and the responding T cells were not required, indicating that HSP70 activation may occur across MHC barriers.
1428 11196165 Besides the MHC-restricted and peptide-dependent activation pathway, HSP70 with no endogenous complexed peptides or HSP70 purified from antigen-negative cells was also able to induce IFN-gamma release by antimelanoma T cells by a MHC-independent mechanism.
1429 11207297 Infection of CD40- or MHC class II-deficient mice induced poor CD8 T cell responses in the intestinal mucosa, but only partially reduced responses in the spleen and liver.
1430 11222495 Treatment of human cancers with an inherent antigen-processing defect due to a loss of peptide transporters (TAP-1 and TAP-2) and/or MHC class I antigen expression remains a considerable challenge.
1431 11222495 There is now an increasing realization that tumor cells with down-regulated expression of TAP and/or MHC class I antigens display strong resistance to cytotoxic T lymphocyte (CTL)-mediated immune control, and often fail to respond to the conventional immunotherapeutic protocols based on active immunization with tumor-associated epitopes (TAE) or adoptive transfer of tumor-specific T cells.
1432 11222495 In the present study, we describe a novel approach based on immunization with either genetically modified tumor cells or naked DNA vectors encoding TAE fused to an endoplasmic reticulum (ER) signal sequence (ER-TAE) which affords protection against challenge by melanoma cells with down-regulated expression of TAP-1/2 and MHC class I antigens.
1433 11222495 These observations provide a new strategy in anti-cancer vaccine design that allows activation of a highly effective and well-defined CTL response against tumors with down-regulated expression of TAP and MHC class I antigens.
1434 11222495 Treatment of human cancers with an inherent antigen-processing defect due to a loss of peptide transporters (TAP-1 and TAP-2) and/or MHC class I antigen expression remains a considerable challenge.
1435 11222495 There is now an increasing realization that tumor cells with down-regulated expression of TAP and/or MHC class I antigens display strong resistance to cytotoxic T lymphocyte (CTL)-mediated immune control, and often fail to respond to the conventional immunotherapeutic protocols based on active immunization with tumor-associated epitopes (TAE) or adoptive transfer of tumor-specific T cells.
1436 11222495 In the present study, we describe a novel approach based on immunization with either genetically modified tumor cells or naked DNA vectors encoding TAE fused to an endoplasmic reticulum (ER) signal sequence (ER-TAE) which affords protection against challenge by melanoma cells with down-regulated expression of TAP-1/2 and MHC class I antigens.
1437 11222495 These observations provide a new strategy in anti-cancer vaccine design that allows activation of a highly effective and well-defined CTL response against tumors with down-regulated expression of TAP and MHC class I antigens.
1438 11222495 Treatment of human cancers with an inherent antigen-processing defect due to a loss of peptide transporters (TAP-1 and TAP-2) and/or MHC class I antigen expression remains a considerable challenge.
1439 11222495 There is now an increasing realization that tumor cells with down-regulated expression of TAP and/or MHC class I antigens display strong resistance to cytotoxic T lymphocyte (CTL)-mediated immune control, and often fail to respond to the conventional immunotherapeutic protocols based on active immunization with tumor-associated epitopes (TAE) or adoptive transfer of tumor-specific T cells.
1440 11222495 In the present study, we describe a novel approach based on immunization with either genetically modified tumor cells or naked DNA vectors encoding TAE fused to an endoplasmic reticulum (ER) signal sequence (ER-TAE) which affords protection against challenge by melanoma cells with down-regulated expression of TAP-1/2 and MHC class I antigens.
1441 11222495 These observations provide a new strategy in anti-cancer vaccine design that allows activation of a highly effective and well-defined CTL response against tumors with down-regulated expression of TAP and MHC class I antigens.
1442 11222495 Treatment of human cancers with an inherent antigen-processing defect due to a loss of peptide transporters (TAP-1 and TAP-2) and/or MHC class I antigen expression remains a considerable challenge.
1443 11222495 There is now an increasing realization that tumor cells with down-regulated expression of TAP and/or MHC class I antigens display strong resistance to cytotoxic T lymphocyte (CTL)-mediated immune control, and often fail to respond to the conventional immunotherapeutic protocols based on active immunization with tumor-associated epitopes (TAE) or adoptive transfer of tumor-specific T cells.
1444 11222495 In the present study, we describe a novel approach based on immunization with either genetically modified tumor cells or naked DNA vectors encoding TAE fused to an endoplasmic reticulum (ER) signal sequence (ER-TAE) which affords protection against challenge by melanoma cells with down-regulated expression of TAP-1/2 and MHC class I antigens.
1445 11222495 These observations provide a new strategy in anti-cancer vaccine design that allows activation of a highly effective and well-defined CTL response against tumors with down-regulated expression of TAP and MHC class I antigens.
1446 11228533 The expression of CD70 and CD80 by gene-modified tumor cells induces an antitumor response depending on the MHC status.
1447 11228533 The expression of costimulatory molecules such as CD70 or CD80 by gene-modified tumor cells has been shown to enhance the antitumor immune response based mainly on T lymphocytes.
1448 11228533 To investigate if coexpression of CD70 and CD80 costimulatory molecules induces comparable antitumor responses in low and high MHC-expressing tumor cells, we used two low immunogenic murine tumor models, the B16.F10 melanoma and the TS/A mammary adenocarcinoma cell lines expressing, respectively, low and high levels of MHC class I molecules.
1449 11228533 Transfection of both CD70 and CD80 genes resulted in an increased capacity of gene-modified tumor cells to costimulate in vitro the proliferation and cytokine production of optimally activated lymphoid cells.
1450 11228533 Coexpression of CD70 and CD80 by the two tumor cell lines, TS/A and B16.F10, resulted in both cases in partial regression of subcutaneous tumors.
1451 11228533 Immunochemical analysis and studies in nude mice showed that, even in the B16.F10 model, T cells had a significant role in the antitumor response induced by combining CD70 and CD80.
1452 11228533 However, rejection of the CD70/CD80-transfected tumor cells appeared more effective in the MHC class I high TS/A model, leading to a protection against parental tumor cells.
1453 11228533 In the two models tested, the injections of irradiated IL-12 and CD70/CD80 gene-modified cells generated an antitumor response to established tumors leading to the slowing down of the tumor growth rate.
1454 11228533 The expression of CD70 and CD80 by gene-modified tumor cells induces an antitumor response depending on the MHC status.
1455 11228533 The expression of costimulatory molecules such as CD70 or CD80 by gene-modified tumor cells has been shown to enhance the antitumor immune response based mainly on T lymphocytes.
1456 11228533 To investigate if coexpression of CD70 and CD80 costimulatory molecules induces comparable antitumor responses in low and high MHC-expressing tumor cells, we used two low immunogenic murine tumor models, the B16.F10 melanoma and the TS/A mammary adenocarcinoma cell lines expressing, respectively, low and high levels of MHC class I molecules.
1457 11228533 Transfection of both CD70 and CD80 genes resulted in an increased capacity of gene-modified tumor cells to costimulate in vitro the proliferation and cytokine production of optimally activated lymphoid cells.
1458 11228533 Coexpression of CD70 and CD80 by the two tumor cell lines, TS/A and B16.F10, resulted in both cases in partial regression of subcutaneous tumors.
1459 11228533 Immunochemical analysis and studies in nude mice showed that, even in the B16.F10 model, T cells had a significant role in the antitumor response induced by combining CD70 and CD80.
1460 11228533 However, rejection of the CD70/CD80-transfected tumor cells appeared more effective in the MHC class I high TS/A model, leading to a protection against parental tumor cells.
1461 11228533 In the two models tested, the injections of irradiated IL-12 and CD70/CD80 gene-modified cells generated an antitumor response to established tumors leading to the slowing down of the tumor growth rate.
1462 11228533 The expression of CD70 and CD80 by gene-modified tumor cells induces an antitumor response depending on the MHC status.
1463 11228533 The expression of costimulatory molecules such as CD70 or CD80 by gene-modified tumor cells has been shown to enhance the antitumor immune response based mainly on T lymphocytes.
1464 11228533 To investigate if coexpression of CD70 and CD80 costimulatory molecules induces comparable antitumor responses in low and high MHC-expressing tumor cells, we used two low immunogenic murine tumor models, the B16.F10 melanoma and the TS/A mammary adenocarcinoma cell lines expressing, respectively, low and high levels of MHC class I molecules.
1465 11228533 Transfection of both CD70 and CD80 genes resulted in an increased capacity of gene-modified tumor cells to costimulate in vitro the proliferation and cytokine production of optimally activated lymphoid cells.
1466 11228533 Coexpression of CD70 and CD80 by the two tumor cell lines, TS/A and B16.F10, resulted in both cases in partial regression of subcutaneous tumors.
1467 11228533 Immunochemical analysis and studies in nude mice showed that, even in the B16.F10 model, T cells had a significant role in the antitumor response induced by combining CD70 and CD80.
1468 11228533 However, rejection of the CD70/CD80-transfected tumor cells appeared more effective in the MHC class I high TS/A model, leading to a protection against parental tumor cells.
1469 11228533 In the two models tested, the injections of irradiated IL-12 and CD70/CD80 gene-modified cells generated an antitumor response to established tumors leading to the slowing down of the tumor growth rate.
1470 11228537 Antitumor effects of the combination therapy with TNF-alpha gene-modified tumor cells and interleukin 12 in a melanoma model in mice.
1471 11228537 FACS analysis of parental B78 melanoma cells and its B78/TNF genetically modified variant showed that a proportion of cells of both cell lines expressed 87-1 (CD80) costimulatory molecule and that the expression of this molecule was increased during incubation with IFN-gamma.
1472 11228537 Moreover, IFN-gamma markedly augmented expression of major histocompatibility class (MHC) class I and II molecules on B78/TNF cells that were primarily MHC class I and II negative with no substantial effect on MHC-negative parental B78 melanoma.
1473 11228537 IFN-gamma also synergized in cytostatic/cytotoxic effects with TNF-alpha against B78 melanoma in vitro.
1474 11228537 The results suggest that, when used therapeutically, IL-12 and a vaccine containing TNF-alpha gene-transduced tumor cells may reciprocally augment their overall antitumor effectiveness by facilitating development of systemic antitumor immunity and by stimulating local effector mechanisms of the tumor destruction.
1475 11251977 Role of Fas ligand expression in promoting escape from immune rejection in a spontaneous tumor model.
1476 11251977 Escape tumors retained rNeu or MHC class I expression but significantly upregulated Fas (CD95, Apo-1) ligand.
1477 11254719 We studied the CTL response induced in HLA-A*0201/K(b) transgenic mice immunized with peptides derived from two melanoma-associated differentiation Ags, the HLA-A*0201-restricted decapeptide Melan-A(26--35) substituted at position 2 and the K(b)-restricted tyrosinase-related protein 2(181--188) T cell epitope.
1478 11254719 Moreover, the CTL response generated against the tyrosinase-related protein 2(181-188) peptide in presence of P40 is associated with tumor protection in two different experimental models and is independent of the presence of CD4(+) T lymphocytes.
1479 11257391 So far an HLA-A*O201 restricted CD8 T cell response has been recorded in the single HLA-A*O201 patient whose tumour was shown to be HPV16 positive.
1480 11260328 When administered with an adjuvant, however, they are capable of inducing a CD8+ T-cell response where antigen recognition is associated with Class I MHC.
1481 11265647 Here we describe that i. m. injection of unmethylated CpG motifs induced the expression of chemokines (monocyte chemotactic protein-1) and MHC class II molecules on myocytes.
1482 11265647 Our results indicate that immunostimulatory DNA sequences (CpG motifs) of DNA vaccines augment synthesis of chemokine by myocytes with subsequent recruitment of inflammatory cells secreting IFN-gamma, a potent cytokine that up-regulates the expression of MHC class II molecules on myocytes.
1483 11265647 A myoblast cell line triple transfected with plasmids encoding MHC class II molecules and an immunodominant CD4 T cell epitope of influenza virus presented the endogenously synthesized peptide and activated specific T cells.
1484 11265647 Here we describe that i. m. injection of unmethylated CpG motifs induced the expression of chemokines (monocyte chemotactic protein-1) and MHC class II molecules on myocytes.
1485 11265647 Our results indicate that immunostimulatory DNA sequences (CpG motifs) of DNA vaccines augment synthesis of chemokine by myocytes with subsequent recruitment of inflammatory cells secreting IFN-gamma, a potent cytokine that up-regulates the expression of MHC class II molecules on myocytes.
1486 11265647 A myoblast cell line triple transfected with plasmids encoding MHC class II molecules and an immunodominant CD4 T cell epitope of influenza virus presented the endogenously synthesized peptide and activated specific T cells.
1487 11265647 Here we describe that i. m. injection of unmethylated CpG motifs induced the expression of chemokines (monocyte chemotactic protein-1) and MHC class II molecules on myocytes.
1488 11265647 Our results indicate that immunostimulatory DNA sequences (CpG motifs) of DNA vaccines augment synthesis of chemokine by myocytes with subsequent recruitment of inflammatory cells secreting IFN-gamma, a potent cytokine that up-regulates the expression of MHC class II molecules on myocytes.
1489 11265647 A myoblast cell line triple transfected with plasmids encoding MHC class II molecules and an immunodominant CD4 T cell epitope of influenza virus presented the endogenously synthesized peptide and activated specific T cells.
1490 11300471 CD8+ T-cell response to NY-ESO-1: relative antigenicity and in vitro immunogenicity of natural and analogue sequences.
1491 11300471 We have shown previously that HLA-A*0201 melanoma patients can frequently develop a CTL response to the cancer testis antigen NY-ESO-1.
1492 11300471 The results of this analysis revealed that, although suboptimal for binding to the HLA-A*0201 molecule, peptide NY-ESO-1 157-165 is, among natural sequences, very efficiently recognized by specific CTL clones derived from three melanoma patients.
1493 11300471 In contrast, peptides NY-ESO-1 157-167 and NY-ESO-1 155-163, which bind very strongly to HLA-A*0201, are recognized less efficiently.
1494 11300471 In agreement with previous data, substitution of peptide NY-ESO-1 157-165 COOH-terminal C with various other amino acids resulted in a significantly increased binding to HLA-A*0201 molecules as well as in an increased CTL recognition, although variable at the clonal level.
1495 11300471 The fine specificity of interaction between peptide NY-ESO-1 C165A, HLA-A*0201, and T-cell receptor was analyzed at the molecular level using a series of variant peptides containing single alanine substitutions.
1496 11300471 CD8+ T-cell response to NY-ESO-1: relative antigenicity and in vitro immunogenicity of natural and analogue sequences.
1497 11300471 We have shown previously that HLA-A*0201 melanoma patients can frequently develop a CTL response to the cancer testis antigen NY-ESO-1.
1498 11300471 The results of this analysis revealed that, although suboptimal for binding to the HLA-A*0201 molecule, peptide NY-ESO-1 157-165 is, among natural sequences, very efficiently recognized by specific CTL clones derived from three melanoma patients.
1499 11300471 In contrast, peptides NY-ESO-1 157-167 and NY-ESO-1 155-163, which bind very strongly to HLA-A*0201, are recognized less efficiently.
1500 11300471 In agreement with previous data, substitution of peptide NY-ESO-1 157-165 COOH-terminal C with various other amino acids resulted in a significantly increased binding to HLA-A*0201 molecules as well as in an increased CTL recognition, although variable at the clonal level.
1501 11300471 The fine specificity of interaction between peptide NY-ESO-1 C165A, HLA-A*0201, and T-cell receptor was analyzed at the molecular level using a series of variant peptides containing single alanine substitutions.
1502 11300471 CD8+ T-cell response to NY-ESO-1: relative antigenicity and in vitro immunogenicity of natural and analogue sequences.
1503 11300471 We have shown previously that HLA-A*0201 melanoma patients can frequently develop a CTL response to the cancer testis antigen NY-ESO-1.
1504 11300471 The results of this analysis revealed that, although suboptimal for binding to the HLA-A*0201 molecule, peptide NY-ESO-1 157-165 is, among natural sequences, very efficiently recognized by specific CTL clones derived from three melanoma patients.
1505 11300471 In contrast, peptides NY-ESO-1 157-167 and NY-ESO-1 155-163, which bind very strongly to HLA-A*0201, are recognized less efficiently.
1506 11300471 In agreement with previous data, substitution of peptide NY-ESO-1 157-165 COOH-terminal C with various other amino acids resulted in a significantly increased binding to HLA-A*0201 molecules as well as in an increased CTL recognition, although variable at the clonal level.
1507 11300471 The fine specificity of interaction between peptide NY-ESO-1 C165A, HLA-A*0201, and T-cell receptor was analyzed at the molecular level using a series of variant peptides containing single alanine substitutions.
1508 11300471 CD8+ T-cell response to NY-ESO-1: relative antigenicity and in vitro immunogenicity of natural and analogue sequences.
1509 11300471 We have shown previously that HLA-A*0201 melanoma patients can frequently develop a CTL response to the cancer testis antigen NY-ESO-1.
1510 11300471 The results of this analysis revealed that, although suboptimal for binding to the HLA-A*0201 molecule, peptide NY-ESO-1 157-165 is, among natural sequences, very efficiently recognized by specific CTL clones derived from three melanoma patients.
1511 11300471 In contrast, peptides NY-ESO-1 157-167 and NY-ESO-1 155-163, which bind very strongly to HLA-A*0201, are recognized less efficiently.
1512 11300471 In agreement with previous data, substitution of peptide NY-ESO-1 157-165 COOH-terminal C with various other amino acids resulted in a significantly increased binding to HLA-A*0201 molecules as well as in an increased CTL recognition, although variable at the clonal level.
1513 11300471 The fine specificity of interaction between peptide NY-ESO-1 C165A, HLA-A*0201, and T-cell receptor was analyzed at the molecular level using a series of variant peptides containing single alanine substitutions.
1514 11300471 CD8+ T-cell response to NY-ESO-1: relative antigenicity and in vitro immunogenicity of natural and analogue sequences.
1515 11300471 We have shown previously that HLA-A*0201 melanoma patients can frequently develop a CTL response to the cancer testis antigen NY-ESO-1.
1516 11300471 The results of this analysis revealed that, although suboptimal for binding to the HLA-A*0201 molecule, peptide NY-ESO-1 157-165 is, among natural sequences, very efficiently recognized by specific CTL clones derived from three melanoma patients.
1517 11300471 In contrast, peptides NY-ESO-1 157-167 and NY-ESO-1 155-163, which bind very strongly to HLA-A*0201, are recognized less efficiently.
1518 11300471 In agreement with previous data, substitution of peptide NY-ESO-1 157-165 COOH-terminal C with various other amino acids resulted in a significantly increased binding to HLA-A*0201 molecules as well as in an increased CTL recognition, although variable at the clonal level.
1519 11300471 The fine specificity of interaction between peptide NY-ESO-1 C165A, HLA-A*0201, and T-cell receptor was analyzed at the molecular level using a series of variant peptides containing single alanine substitutions.
1520 11312024 Contribution of MHC class I-dependent immune mechanisms induced by attenuated recombinant Salmonella typhimurium secreting superoxide dismutase to protection against murine listeriosis.
1521 11312024 TAP1-deficient mice (devoid of most CD8 T cells) vaccinated with this rSalmonella SODs strain succumbed to lethal L. monocytogenes challenge, whereas C57BL/6 mice were protected by this vaccine.
1522 11312024 Moreover, vaccination of H-2I-Abeta-deficient mice (lacking major histocompatibility class (MHC) II molecules and thus devoid of mature CD4 TCR-alphabeta cells), of TAP1-deficient as well as of beta2microglobulin-deficient mice (devoid of conventional CD8 T cells) with a sublethal dose of L. monocytogenes and subsequent challenge with rSalmonella control or SODs strain revealed contribution of both MHC class I- and MHC class II-dependent immune mechanisms to the control of secondary Salmonella infection.
1523 11312024 Finally, the clearance of rSalmonella SODs bacteria was achieved in TAP1-deficient animals vaccinated with L. monocytogenes.
1524 11312024 Contribution of MHC class I-dependent immune mechanisms induced by attenuated recombinant Salmonella typhimurium secreting superoxide dismutase to protection against murine listeriosis.
1525 11312024 TAP1-deficient mice (devoid of most CD8 T cells) vaccinated with this rSalmonella SODs strain succumbed to lethal L. monocytogenes challenge, whereas C57BL/6 mice were protected by this vaccine.
1526 11312024 Moreover, vaccination of H-2I-Abeta-deficient mice (lacking major histocompatibility class (MHC) II molecules and thus devoid of mature CD4 TCR-alphabeta cells), of TAP1-deficient as well as of beta2microglobulin-deficient mice (devoid of conventional CD8 T cells) with a sublethal dose of L. monocytogenes and subsequent challenge with rSalmonella control or SODs strain revealed contribution of both MHC class I- and MHC class II-dependent immune mechanisms to the control of secondary Salmonella infection.
1527 11312024 Finally, the clearance of rSalmonella SODs bacteria was achieved in TAP1-deficient animals vaccinated with L. monocytogenes.
1528 11329066 DCs are unique in their ability to process exogenous antigens via the major histocompatibility complex (MHC) class I pathway as well as in their ability to activate naive, antigen-specific CD8+ and CD4+ T cells.
1529 11359856 IFN-gamma-inducible protein-10 is essential for the generation of a protective tumor-specific CD8 T cell response induced by single-chain IL-12 gene therapy.
1530 11359856 Here, we demonstrate that the induction of tumor-protective immunity by IL-12 in a murine neuroblastoma model depends entirely on the CXC chemokine IFN-gamma-inducible protein 10 (IP-10).
1531 11359856 This was established by in vivo depletion of IP-10 with mAbs in mice vaccinated against NXS2 neuroblastoma by gene therapy with a linearized, single-chain (sc) version of the heterodimeric cytokine IL-12 (scIL-12).
1532 11359856 These findings were extended by data demonstrating that IP-10 is directly involved in the generation of a tumor-protective CD8+ T cell-mediated immune response during the early immunization phase.
1533 11359856 Second, CD8+ T cell-mediated MHC class I Ag-restricted tumor cell lysis was inhibited in such mice.
1534 11359856 Third, intracellular IFN-gamma expressed by proliferating CD8+ T cells was substantially inhibited in IP-10-depleted, scIL-12 NXS2-vaccinated mice.
1535 11390619 Differential incorporation of CD45, CD80 (B7-1), CD86 (B7-2), and major histocompatibility complex class I and II molecules into human immunodeficiency virus type 1 virions and microvesicles: implications for viral pathogenesis and immune regulation.
1536 11390619 Because T-cell receptor engagement of major histocompatibility complex (MHC) molecules in the absence of costimulation mediated via CD28 binding to CD80 (B7-1) or CD86 (B7-2) can lead to anergy or apoptosis, we determined whether HIV type 1 (HIV-1) virions incorporated MHC class I (MHC-I), MHC-II, CD80, or CD86.
1537 11390619 HIV infection increased MHC-II expression on T- and B-cell lines, macrophages, and peripheral blood mononclear cells (PBMC) but did not significantly alter the expression of CD80 or CD86.
1538 11390619 HIV virions derived from all MHC-II-positive cell types incorporated high levels of MHC-II, and both virions and microvesicles preferentially incorporated CD86 compared to CD80.
1539 11394496 MHC class II-restricted tumor antigens recognized by CD4+ T cells: new strategies for cancer vaccine design.
1540 11394496 This finding has led to the identification and characterization of tumor-associated antigens recognized by CD8+ TIL.
1541 11394496 These data suggest that it may be necessary to engage both CD4+ and CD8+ T cells for more effective antitumor immunotherapy.
1542 11394496 In this report, we review emerging molecular approaches in cloning major histocompatibility complex (MHC) class II restricted tumor antigens recognized by CD4+ T cells as well as approaches to identify new MHC class II-restricted epitopes from known tumor antigens recognized by CD8+ cytotoxic T lymphocytes and/or antibodies.
1543 11394496 More importantly, the discovery of MHC class II-restricted tumor antigens has provided opportunities for developing a new generation of cancer vaccines aimed at eliciting both CD4+ and CD8+ T-cell responses against tumor.
1544 11394496 MHC class II-restricted tumor antigens recognized by CD4+ T cells: new strategies for cancer vaccine design.
1545 11394496 This finding has led to the identification and characterization of tumor-associated antigens recognized by CD8+ TIL.
1546 11394496 These data suggest that it may be necessary to engage both CD4+ and CD8+ T cells for more effective antitumor immunotherapy.
1547 11394496 In this report, we review emerging molecular approaches in cloning major histocompatibility complex (MHC) class II restricted tumor antigens recognized by CD4+ T cells as well as approaches to identify new MHC class II-restricted epitopes from known tumor antigens recognized by CD8+ cytotoxic T lymphocytes and/or antibodies.
1548 11394496 More importantly, the discovery of MHC class II-restricted tumor antigens has provided opportunities for developing a new generation of cancer vaccines aimed at eliciting both CD4+ and CD8+ T-cell responses against tumor.
1549 11394496 MHC class II-restricted tumor antigens recognized by CD4+ T cells: new strategies for cancer vaccine design.
1550 11394496 This finding has led to the identification and characterization of tumor-associated antigens recognized by CD8+ TIL.
1551 11394496 These data suggest that it may be necessary to engage both CD4+ and CD8+ T cells for more effective antitumor immunotherapy.
1552 11394496 In this report, we review emerging molecular approaches in cloning major histocompatibility complex (MHC) class II restricted tumor antigens recognized by CD4+ T cells as well as approaches to identify new MHC class II-restricted epitopes from known tumor antigens recognized by CD8+ cytotoxic T lymphocytes and/or antibodies.
1553 11394496 More importantly, the discovery of MHC class II-restricted tumor antigens has provided opportunities for developing a new generation of cancer vaccines aimed at eliciting both CD4+ and CD8+ T-cell responses against tumor.
1554 11395634 MHC Class II-Restricted Tumor Antigens Recognized by CD4+ T Cells: New Strategies for Cancer Vaccine Design.
1555 11395634 This finding has led to the identification and characterization of tumor-associated antigens recognized by CD8+ TIL.
1556 11395634 These data suggest that it may be necessary to engage both CD4+ and CD8+ T cells for more effective antitumor immunotherapy.
1557 11395634 In this report, we review emerging molecular approaches in cloning major histocompatibility complex (MHC) class II restricted tumor antigens recognized by CD4+ T cells as well as approaches to identify new MHC class II-restricted epitopes from known tumor antigens recognized by CD8+ cytotoxic T lymphocytes and/or antibodies.
1558 11395634 More importantly, the discovery of MHC class II-restricted tumor antigens has provided opportunities for developing a new generation of cancer vaccines aimed at eliciting both CD4+ and CD8+ T-cell responses against tumor.
1559 11395634 MHC Class II-Restricted Tumor Antigens Recognized by CD4+ T Cells: New Strategies for Cancer Vaccine Design.
1560 11395634 This finding has led to the identification and characterization of tumor-associated antigens recognized by CD8+ TIL.
1561 11395634 These data suggest that it may be necessary to engage both CD4+ and CD8+ T cells for more effective antitumor immunotherapy.
1562 11395634 In this report, we review emerging molecular approaches in cloning major histocompatibility complex (MHC) class II restricted tumor antigens recognized by CD4+ T cells as well as approaches to identify new MHC class II-restricted epitopes from known tumor antigens recognized by CD8+ cytotoxic T lymphocytes and/or antibodies.
1563 11395634 More importantly, the discovery of MHC class II-restricted tumor antigens has provided opportunities for developing a new generation of cancer vaccines aimed at eliciting both CD4+ and CD8+ T-cell responses against tumor.
1564 11395634 MHC Class II-Restricted Tumor Antigens Recognized by CD4+ T Cells: New Strategies for Cancer Vaccine Design.
1565 11395634 This finding has led to the identification and characterization of tumor-associated antigens recognized by CD8+ TIL.
1566 11395634 These data suggest that it may be necessary to engage both CD4+ and CD8+ T cells for more effective antitumor immunotherapy.
1567 11395634 In this report, we review emerging molecular approaches in cloning major histocompatibility complex (MHC) class II restricted tumor antigens recognized by CD4+ T cells as well as approaches to identify new MHC class II-restricted epitopes from known tumor antigens recognized by CD8+ cytotoxic T lymphocytes and/or antibodies.
1568 11395634 More importantly, the discovery of MHC class II-restricted tumor antigens has provided opportunities for developing a new generation of cancer vaccines aimed at eliciting both CD4+ and CD8+ T-cell responses against tumor.
1569 11431355 Peptide-specific T-cell lines could be generated from two of the four peptides, p199-213 and p228-242, that also proliferated in response to PAP protein stimulation.
1570 11431355 The ability of these two peptides to elicit PAP-specific Th responses suggests that they represent naturally processed PAP-specific MHC class II epitopes.
1571 11439158 Interestingly, studies in the present report revealed that antigen encapsulated in yeast lipid liposomes could be successfully delivered simultaneously into the cytosolic as well as endosomal processing pathways of APCs, leading to the generation of both CD4+ T helper and CD8+ cytotoxic T cells.
1572 11439158 In contrast, encapsulation of same antigen in egg phosphatidyl-choline (PC) liposomes, just like its free form, has inefficient access to the cytosolic pathway of major histocompatibility complex (MHC) I dependent antigen presentation and failed to generate antigen specific CD8+ cytotoxic T-cell response.
1573 11441073 The ability of a specific MHC/peptide mAb to inhibit and divert the CD8(+) T cell response holds implications for vaccine design and approaches to modulate the immune response in autoimmunity.
1574 11443550 Both interferon (IFN)-gamma secretion by CD8(+) T cells and the frequency of human leukocyte antigen (HLA)-tetramer-positive T cells in HLA-A*0201-positive HIV-infected subjects correlated with CMV-specific cytolysis.
1575 11449353 Comprehensive analysis of the frequency of recognition of melanoma-associated antigen (MAA) by CD8 melanoma infiltrating lymphocytes (TIL): implications for immunotherapy.
1576 11449353 Melanosomal proteins were recognized by 19 TIL populations and the most prominent responses against these proteins were directed against Melan-A/MART-1 (mainly in association with HLA-A*0201) and gp100 (in association with diverse HLA contexts).
1577 11457540 Specifically, the processing of the P. berghei CS 9-mer as an exogenous antigen and its presentation via MHC class I molecules to CD8+ T cells led to an immune response that is an in vitro correlate of protection against preerythrocytic malaria.
1578 11459172 In order to construct an immunogenic cellular vaccine, we transduced three HLA-A*0201 human melanoma lines, selected for expression of classes I and II HLA, adhesion molecules and the T cell-defined melanoma antigens Melan/MART-1, gp100 and tyrosinase, with both interleukin-2 (IL-2) and B7-1 genes by the use of a polycistronic retroviral vector.
1579 11459172 From a functional point of view, expression of both genes in melanoma lines: (1) improved the response of anti-melanoma cytotoxic T lymphocytes (CTL) over singly transduced or untransduced melanoma cells when subthreshold levels of MHC-peptide complexes were expressed by melanoma cells; (2) conferred a distinct advantage in the ability to stimulate cytotoxicity and interferon-gamma release by autologous and/or HLA-A*0201-compatible allogeneic lymphocytes; (3) allowed the generation of a high number of specific CTL by in vitro stimulation of lymphocytes of HLA-A*0201-melanoma patients.
1580 11459172 In order to construct an immunogenic cellular vaccine, we transduced three HLA-A*0201 human melanoma lines, selected for expression of classes I and II HLA, adhesion molecules and the T cell-defined melanoma antigens Melan/MART-1, gp100 and tyrosinase, with both interleukin-2 (IL-2) and B7-1 genes by the use of a polycistronic retroviral vector.
1581 11459172 From a functional point of view, expression of both genes in melanoma lines: (1) improved the response of anti-melanoma cytotoxic T lymphocytes (CTL) over singly transduced or untransduced melanoma cells when subthreshold levels of MHC-peptide complexes were expressed by melanoma cells; (2) conferred a distinct advantage in the ability to stimulate cytotoxicity and interferon-gamma release by autologous and/or HLA-A*0201-compatible allogeneic lymphocytes; (3) allowed the generation of a high number of specific CTL by in vitro stimulation of lymphocytes of HLA-A*0201-melanoma patients.
1582 11462005 This property has been exploited to design recombinant CyaA toxoids capable of delivering major histocompatibility complex (MHC) class I-restricted CD8(+) T-cell epitopes into antigen-presenting cells and to induce specific CD8(+) cytotoxic T-lymphocyte (CTL) responses in vivo.
1583 11462005 These results highlight the potency of the adenylate cyclase vector for induction of protective CTL responses with multiple specificity and/or broad MHC restriction.
1584 11462005 This property has been exploited to design recombinant CyaA toxoids capable of delivering major histocompatibility complex (MHC) class I-restricted CD8(+) T-cell epitopes into antigen-presenting cells and to induce specific CD8(+) cytotoxic T-lymphocyte (CTL) responses in vivo.
1585 11462005 These results highlight the potency of the adenylate cyclase vector for induction of protective CTL responses with multiple specificity and/or broad MHC restriction.
1586 11466405 Cocultures of ALVAC MART-1-infected and uninfected DC are able to induce MART-1-specific T cell immune responses, as assessed by HLA class I/peptide tetramer binding, IFN-gamma ELISPOT assays, and cytotoxicity tests.
1587 11477558 Our data showed that phagocytosis of apoptotic/necrotic tumor cells resulted in maturation of DCs with up-regulated expression of proinflammatory cytokines [interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha, interferon-gamma and granulocyte-macrophage colony-stimulating factor], chemokines (MIP-1alpha, MIP-1beta and MIP-2), the CC chemokine receptor CCR7 and the cell surface molecules (MHC class II, CD11b, CD40 and CD86), and down-regulated expression of the CC chemokine receptors CCR2 and CCR5.
1588 11507070 We demonstrate that a mouse-human chimeric anti-ganglioside GD2-interleukin (IL)-2 fusion protein (ch14.18-IL2) substantially amplifies tumor-protective immunity against murine melanoma induced by an autologous oral DNA vaccine containing the murine ubiquitin gene fused to murine melanoma peptide epitopes gp100(25-35) and TRP-2(181-188).
1589 11507070 The tumor-protective immunity was mediated by MHC class I antigen- restricted CD8(+) T cells together with CD4(+) T cell help, which was required only for tumor cell killing in the effector phase of the immune response.
1590 11507070 The immunological mechanisms involved in this antitumor effect were suggested by a decisively increased secretion of tumor necrosis factor alpha TNFTnTNa and IFN-gamma from CD4(+) and CD8(+) T cells and a markedly up-regulated expression on CD8(+) T cells of high-affinity IL-2 receptor alpha chain (CD25), costimulatory molecule CD28, and adhesion molecule lymphocyte function-associated antigen-2 (LFA-2/CD2).
1591 11509592 This was not restored by adding exogenous beta(2)-microglobulin to stabilize the MHC complex on the cell surface.
1592 11509618 HLA class I restriction and cytotoxic activity were confirmed after isolation of peptide-specific CD8(+) T cell lines.
1593 11522640 Eighteen HLA A*0201(+) patients with metastatic melanoma received injections s.c. of CD34(+)progenitor-derived autologous dendritic cells (DCs), which included Langerhans cells.
1594 11522640 DCs were pulsed with peptides derived from four melanoma antigens [(MelAgs) MelanA/MART-1, tyrosinase, MAGE-3, and gp100], as well as influenza matrix peptide (Flu-MP) and keyhole limpet hemocyanin (KLH) as control antigens.
1595 11527700 T Lymphocytes infiltrating various tumour types express the MHC class II ligand lymphocyte activation gene-3 (LAG-3): role of LAG-3/MHC class II interactions in cell-cell contacts.
1596 11527700 The product of the Lymphocyte Activation Gene-3 (LAG-3, CD223) is a high affinity MHC class II ligand expressed by activated CD4(+) and CD8(+) T cells, which can associate with the T cell receptor (TCR) and downregulate TCR signalling in vitro.
1597 11527700 We have also reported that a soluble mLAG-3Ig fusion protein works as a vaccine adjuvant in vivo in mice, enhancing Th1 and CD8 T cell responses.
1598 11527700 Here, we report that LAG-3 expression was found, using fluorescent activated cell sorting (FACS) analysis, on 11-48% of human tumour-infiltrating lymphocytes (TILs) isolated from eight freshly dissociated renal cell carcinomas (RCCs), and was restricted mostly to CD8(+) cells.
1599 11527700 Since not only antigen presenting cells (APCs), but also TILs themselves strongly express major histocompatibility complex (MHC) class II, we firstly investigated whether LAG-3/MHC class II T-T cell contacts might influence tumour cell recognition.
1600 11527700 In contrast, MHC class II engagement by LAG-3Ig was found to enhance the capacity of immature dendritic cells to stimulate naive T cell proliferation and IL-12-dependent IFN-gamma production by T cells in vitro.
1601 11527700 These results therefore provide support for a role for TIL-expressed LAG-3 in the engagement of class II molecules on APCs, thereby contributing to APC activation and Th1/Tc1 commitment, without downregulating cytotoxicity.
1602 11527700 T Lymphocytes infiltrating various tumour types express the MHC class II ligand lymphocyte activation gene-3 (LAG-3): role of LAG-3/MHC class II interactions in cell-cell contacts.
1603 11527700 The product of the Lymphocyte Activation Gene-3 (LAG-3, CD223) is a high affinity MHC class II ligand expressed by activated CD4(+) and CD8(+) T cells, which can associate with the T cell receptor (TCR) and downregulate TCR signalling in vitro.
1604 11527700 We have also reported that a soluble mLAG-3Ig fusion protein works as a vaccine adjuvant in vivo in mice, enhancing Th1 and CD8 T cell responses.
1605 11527700 Here, we report that LAG-3 expression was found, using fluorescent activated cell sorting (FACS) analysis, on 11-48% of human tumour-infiltrating lymphocytes (TILs) isolated from eight freshly dissociated renal cell carcinomas (RCCs), and was restricted mostly to CD8(+) cells.
1606 11527700 Since not only antigen presenting cells (APCs), but also TILs themselves strongly express major histocompatibility complex (MHC) class II, we firstly investigated whether LAG-3/MHC class II T-T cell contacts might influence tumour cell recognition.
1607 11527700 In contrast, MHC class II engagement by LAG-3Ig was found to enhance the capacity of immature dendritic cells to stimulate naive T cell proliferation and IL-12-dependent IFN-gamma production by T cells in vitro.
1608 11527700 These results therefore provide support for a role for TIL-expressed LAG-3 in the engagement of class II molecules on APCs, thereby contributing to APC activation and Th1/Tc1 commitment, without downregulating cytotoxicity.
1609 11527700 T Lymphocytes infiltrating various tumour types express the MHC class II ligand lymphocyte activation gene-3 (LAG-3): role of LAG-3/MHC class II interactions in cell-cell contacts.
1610 11527700 The product of the Lymphocyte Activation Gene-3 (LAG-3, CD223) is a high affinity MHC class II ligand expressed by activated CD4(+) and CD8(+) T cells, which can associate with the T cell receptor (TCR) and downregulate TCR signalling in vitro.
1611 11527700 We have also reported that a soluble mLAG-3Ig fusion protein works as a vaccine adjuvant in vivo in mice, enhancing Th1 and CD8 T cell responses.
1612 11527700 Here, we report that LAG-3 expression was found, using fluorescent activated cell sorting (FACS) analysis, on 11-48% of human tumour-infiltrating lymphocytes (TILs) isolated from eight freshly dissociated renal cell carcinomas (RCCs), and was restricted mostly to CD8(+) cells.
1613 11527700 Since not only antigen presenting cells (APCs), but also TILs themselves strongly express major histocompatibility complex (MHC) class II, we firstly investigated whether LAG-3/MHC class II T-T cell contacts might influence tumour cell recognition.
1614 11527700 In contrast, MHC class II engagement by LAG-3Ig was found to enhance the capacity of immature dendritic cells to stimulate naive T cell proliferation and IL-12-dependent IFN-gamma production by T cells in vitro.
1615 11527700 These results therefore provide support for a role for TIL-expressed LAG-3 in the engagement of class II molecules on APCs, thereby contributing to APC activation and Th1/Tc1 commitment, without downregulating cytotoxicity.
1616 11527700 T Lymphocytes infiltrating various tumour types express the MHC class II ligand lymphocyte activation gene-3 (LAG-3): role of LAG-3/MHC class II interactions in cell-cell contacts.
1617 11527700 The product of the Lymphocyte Activation Gene-3 (LAG-3, CD223) is a high affinity MHC class II ligand expressed by activated CD4(+) and CD8(+) T cells, which can associate with the T cell receptor (TCR) and downregulate TCR signalling in vitro.
1618 11527700 We have also reported that a soluble mLAG-3Ig fusion protein works as a vaccine adjuvant in vivo in mice, enhancing Th1 and CD8 T cell responses.
1619 11527700 Here, we report that LAG-3 expression was found, using fluorescent activated cell sorting (FACS) analysis, on 11-48% of human tumour-infiltrating lymphocytes (TILs) isolated from eight freshly dissociated renal cell carcinomas (RCCs), and was restricted mostly to CD8(+) cells.
1620 11527700 Since not only antigen presenting cells (APCs), but also TILs themselves strongly express major histocompatibility complex (MHC) class II, we firstly investigated whether LAG-3/MHC class II T-T cell contacts might influence tumour cell recognition.
1621 11527700 In contrast, MHC class II engagement by LAG-3Ig was found to enhance the capacity of immature dendritic cells to stimulate naive T cell proliferation and IL-12-dependent IFN-gamma production by T cells in vitro.
1622 11527700 These results therefore provide support for a role for TIL-expressed LAG-3 in the engagement of class II molecules on APCs, thereby contributing to APC activation and Th1/Tc1 commitment, without downregulating cytotoxicity.
1623 11536162 Lack of tumor recognition by hTERT peptide 540-548-specific CD8(+) T cells from melanoma patients reveals inefficient antigen processing.
1624 11536162 The wide expression of the human telomerase catalytic subunit (hTERT) in tumors makes it an interesting candidate vaccine for cancer. hTERT-derived peptide 540-548 (hTERT(540)) has been recently shown to be recognized in an HLA-A*0201-restricted fashion by T cell lines derived from peptide-stimulated peripheral blood mononuclear cells (PBMC) from healthy donors.
1625 11536162 As a first step to the inclusion of this peptide in immunotherapy clinical trials, it is crucial to assess hTERT(540)-specific T cell reactivity in cancer patients as well as the ability of hTERT-specific CD8(+) T lymphocytes to recognize and lyse hTERT-expressing target cells.
1626 11536162 Here, we have analyzed the CD8(+) T cell response to peptide hTERT(540) in HLA-A*0201 melanoma patients by using fluorescent HLA-A*0201/hTERT(540) peptide tetramers.
1627 11536162 HLA-A*0201/hTERT(540) tetramer(+) CD8(+) T cells were readily detected in peptide-stimulated PBMC from a significant proportion of patients and could be isolated by tetramer-guided cell sorting. hTERT(540)-specific CD8(+) T cells were able to specifically recognize HLA-A*0201 cells either pulsed with peptide or transiently transfected with a minigene encoding the minimal epitope.
1628 11536162 Lack of tumor recognition by hTERT peptide 540-548-specific CD8(+) T cells from melanoma patients reveals inefficient antigen processing.
1629 11536162 The wide expression of the human telomerase catalytic subunit (hTERT) in tumors makes it an interesting candidate vaccine for cancer. hTERT-derived peptide 540-548 (hTERT(540)) has been recently shown to be recognized in an HLA-A*0201-restricted fashion by T cell lines derived from peptide-stimulated peripheral blood mononuclear cells (PBMC) from healthy donors.
1630 11536162 As a first step to the inclusion of this peptide in immunotherapy clinical trials, it is crucial to assess hTERT(540)-specific T cell reactivity in cancer patients as well as the ability of hTERT-specific CD8(+) T lymphocytes to recognize and lyse hTERT-expressing target cells.
1631 11536162 Here, we have analyzed the CD8(+) T cell response to peptide hTERT(540) in HLA-A*0201 melanoma patients by using fluorescent HLA-A*0201/hTERT(540) peptide tetramers.
1632 11536162 HLA-A*0201/hTERT(540) tetramer(+) CD8(+) T cells were readily detected in peptide-stimulated PBMC from a significant proportion of patients and could be isolated by tetramer-guided cell sorting. hTERT(540)-specific CD8(+) T cells were able to specifically recognize HLA-A*0201 cells either pulsed with peptide or transiently transfected with a minigene encoding the minimal epitope.
1633 11536162 Lack of tumor recognition by hTERT peptide 540-548-specific CD8(+) T cells from melanoma patients reveals inefficient antigen processing.
1634 11536162 The wide expression of the human telomerase catalytic subunit (hTERT) in tumors makes it an interesting candidate vaccine for cancer. hTERT-derived peptide 540-548 (hTERT(540)) has been recently shown to be recognized in an HLA-A*0201-restricted fashion by T cell lines derived from peptide-stimulated peripheral blood mononuclear cells (PBMC) from healthy donors.
1635 11536162 As a first step to the inclusion of this peptide in immunotherapy clinical trials, it is crucial to assess hTERT(540)-specific T cell reactivity in cancer patients as well as the ability of hTERT-specific CD8(+) T lymphocytes to recognize and lyse hTERT-expressing target cells.
1636 11536162 Here, we have analyzed the CD8(+) T cell response to peptide hTERT(540) in HLA-A*0201 melanoma patients by using fluorescent HLA-A*0201/hTERT(540) peptide tetramers.
1637 11536162 HLA-A*0201/hTERT(540) tetramer(+) CD8(+) T cells were readily detected in peptide-stimulated PBMC from a significant proportion of patients and could be isolated by tetramer-guided cell sorting. hTERT(540)-specific CD8(+) T cells were able to specifically recognize HLA-A*0201 cells either pulsed with peptide or transiently transfected with a minigene encoding the minimal epitope.
1638 11560772 DNA immunization of HLA transgenic mice with a plasmid expressing mycobacterial heat shock protein 65 results in HLA class I- and II-restricted T cell responses that can be augmented by cytokines.
1639 11560772 To test the ability to induce HLA-restricted T cell immune response against a mycobacterial antigen in humans by pDNA vaccination, we have used transgenic mice that express HLA class I (A*0201/Kb) or HLA class II (DRB1*0301) molecules. pDNA immunization with mycobacterial heat shock protein 65 (Mhsp65)-expressing plasmid (P3M.65) resulted in HLA-II-restricted, Ag-specific T cell-mediated immune responses characterized by proliferation and cytokine production.
1640 11560772 DNA immunization of HLA transgenic mice with a plasmid expressing mycobacterial heat shock protein 65 results in HLA class I- and II-restricted T cell responses that can be augmented by cytokines.
1641 11560772 To test the ability to induce HLA-restricted T cell immune response against a mycobacterial antigen in humans by pDNA vaccination, we have used transgenic mice that express HLA class I (A*0201/Kb) or HLA class II (DRB1*0301) molecules. pDNA immunization with mycobacterial heat shock protein 65 (Mhsp65)-expressing plasmid (P3M.65) resulted in HLA-II-restricted, Ag-specific T cell-mediated immune responses characterized by proliferation and cytokine production.
1642 11562534 Pretreatment of UV-HCMV with trypsin or monoclonal antibody reactive with the envelope glycoprotein gB reduced the increase in HLA class I expression on the HFF cell surface by UV-HCMV.
1643 11571579 We demonstrate that destruction of antigen- expressing myocytes following i.m. injection of a DNA vaccine is dependent on major histocompatibility complex (MHC) class II restricted CD4+ T cell activation, but is not mediated solely by MHC I-restricted or perforin-mediated lysis and appears to have a component that is antibody-mediated.
1644 11578512 A human ovarian carcinoma cell line (UCI-107) was genetically engineered to secrete the cytokine granulocyte-macrophage colony stimulating factor (GM-CSF), by retroviral medicated gene transduction.
1645 11578512 Like the parental cell line UCI-107, UCI-107M GM-CSF-MPS cells expressed MHC class I and Her2/Neu surface antigens but did not express detectable MHC class II, ICAM-1 or CA-125.
1646 11578952 Herein, we will discuss, with special emphasis on MUC1, unusual features of MUC1 peptide binding to MHC class I, obtained from vaccine studies including a MUC1 peptide mimic and the crystal structures of low and high affinity peptides lacking canonical anchor motifs in complex with H-2Kb.
1647 11580226 In the current study, we examined the capacity of DC to elicit CD8+ cytotoxic T lymphocyte (CTL) reactivity against an HLA-A*0201-restricted HIV-1 reverse transcriptase (pol) epitope (residues 476-484) and two naturally occurring variants.
1648 11580228 A chimeric construct of an MHC class II binding peptide from the c-erb oncogene (Her-2/neu) containing the N-terminal flanking region of CLIP elicited potent antitumor activity against a Her-2/neu-positive tumor in a rat model system.
1649 11580228 The induction of effective antitumor immunity, however, required presentation of the chimeric peptide construct on irradiated tumor cells or the peptide construct in concert with a Her-2/neu MHC class I-restricted peptide from Her-2/neu.
1650 11580228 Additionally, in vitro analysis revealed that immunization with the parent peptide resulted in a weak immune response to the unmodified peptide consisting of both type 1 (IL-2, IFN-gamma) and type 2 (IL-4, IL-10) cytokine-producing cells analyzed by RT-PCR (qualitative and quantitative) and by limiting dilution assay.
1651 11580228 A chimeric construct of an MHC class II binding peptide from the c-erb oncogene (Her-2/neu) containing the N-terminal flanking region of CLIP elicited potent antitumor activity against a Her-2/neu-positive tumor in a rat model system.
1652 11580228 The induction of effective antitumor immunity, however, required presentation of the chimeric peptide construct on irradiated tumor cells or the peptide construct in concert with a Her-2/neu MHC class I-restricted peptide from Her-2/neu.
1653 11580228 Additionally, in vitro analysis revealed that immunization with the parent peptide resulted in a weak immune response to the unmodified peptide consisting of both type 1 (IL-2, IFN-gamma) and type 2 (IL-4, IL-10) cytokine-producing cells analyzed by RT-PCR (qualitative and quantitative) and by limiting dilution assay.
1654 11581168 Generation of cytotoxic T lymphocytes by MHC class I ligands fused to heat shock cognate protein 70.
1655 11581168 In addition, mycobacterial heat shock protein 70 covalently fused to ovalbumin (OVA)-derived fragments has been shown to generate MHC class I-restricted CTL responses.
1656 11581168 CD4(+) T cells were not required for the priming of CD8(+) T cells and vaccination with bone marrow-derived dendritic cells pulsed with hsc70 fusion proteins also elicited CTL responses.
1657 11581168 Generation of cytotoxic T lymphocytes by MHC class I ligands fused to heat shock cognate protein 70.
1658 11581168 In addition, mycobacterial heat shock protein 70 covalently fused to ovalbumin (OVA)-derived fragments has been shown to generate MHC class I-restricted CTL responses.
1659 11581168 CD4(+) T cells were not required for the priming of CD8(+) T cells and vaccination with bone marrow-derived dendritic cells pulsed with hsc70 fusion proteins also elicited CTL responses.
1660 11581386 The ability to monitor vaccine-elicited CD8(+) cytotoxic T-lymphocyte (CTL) responses in simian immunodeficiency virus (SIV)- and simian-human immunodeficiency virus (SHIV)-infected rhesus monkeys has been limited by our knowledge of viral epitopes predictably presented to those lymphocytes by common rhesus monkey MHC class I alleles.
1661 11581386 We now define an SIV and SHIV Nef CTL epitope (YTSGPGIRY) that is presented to CD8(+) T lymphocytes by the common rhesus monkey MHC class I molecule Mamu-A*02.
1662 11581386 All seven infected Mamu-A*02(+) monkeys evaluated demonstrated this response, and peptide-stimulated interferon gamma Elispot assays indicated that the response represents a large proportion of the entire CD8(+) T-lymphocyte SIV- or SHIV-specific immune response of these animals.
1663 11581386 The ability to monitor vaccine-elicited CD8(+) cytotoxic T-lymphocyte (CTL) responses in simian immunodeficiency virus (SIV)- and simian-human immunodeficiency virus (SHIV)-infected rhesus monkeys has been limited by our knowledge of viral epitopes predictably presented to those lymphocytes by common rhesus monkey MHC class I alleles.
1664 11581386 We now define an SIV and SHIV Nef CTL epitope (YTSGPGIRY) that is presented to CD8(+) T lymphocytes by the common rhesus monkey MHC class I molecule Mamu-A*02.
1665 11581386 All seven infected Mamu-A*02(+) monkeys evaluated demonstrated this response, and peptide-stimulated interferon gamma Elispot assays indicated that the response represents a large proportion of the entire CD8(+) T-lymphocyte SIV- or SHIV-specific immune response of these animals.
1666 11591745 HIV envelope protein inhibits MHC class I presentation of a cytomegalovirus protective epitope.
1667 11591745 CTL recognize peptides that derive from viral protein Ags by proteolytic processing and are presented by MHC class I molecules.
1668 11591745 Also, point mutants of the presenting MHC class I molecule differed in their competition pattern.
1669 11591745 We conclude that, although not the rule, in certain combinations there is interference between different Ags expressed in the same cell and presented by the same MHC class I allele.
1670 11591745 HIV envelope protein inhibits MHC class I presentation of a cytomegalovirus protective epitope.
1671 11591745 CTL recognize peptides that derive from viral protein Ags by proteolytic processing and are presented by MHC class I molecules.
1672 11591745 Also, point mutants of the presenting MHC class I molecule differed in their competition pattern.
1673 11591745 We conclude that, although not the rule, in certain combinations there is interference between different Ags expressed in the same cell and presented by the same MHC class I allele.
1674 11591745 HIV envelope protein inhibits MHC class I presentation of a cytomegalovirus protective epitope.
1675 11591745 CTL recognize peptides that derive from viral protein Ags by proteolytic processing and are presented by MHC class I molecules.
1676 11591745 Also, point mutants of the presenting MHC class I molecule differed in their competition pattern.
1677 11591745 We conclude that, although not the rule, in certain combinations there is interference between different Ags expressed in the same cell and presented by the same MHC class I allele.
1678 11591745 HIV envelope protein inhibits MHC class I presentation of a cytomegalovirus protective epitope.
1679 11591745 CTL recognize peptides that derive from viral protein Ags by proteolytic processing and are presented by MHC class I molecules.
1680 11591745 Also, point mutants of the presenting MHC class I molecule differed in their competition pattern.
1681 11591745 We conclude that, although not the rule, in certain combinations there is interference between different Ags expressed in the same cell and presented by the same MHC class I allele.
1682 11606135 Major histocompatibility complex class II (MHC II) protein binding and antigen specific activation of CD4+ "helper" T cells are demonstrated with peptides composed of the antigenic hen egg ovalbumin 325-339 peptide (OVA) substituted with azaamino acids.
1683 11672905 This vaccine, delivered by oral gavage with an attenuated strain of Salmonella typhimurium (SL7207), and boosted with an antibody-IL2 fusion protein, induced tumor-protective immunity mediated by MHC class I antigen-restricted CD8(+) T cells, resulting in eradication of subcutaneous tumors in 100% of mice and prevention of experimental pulmonary metastases in 75% of experimental animals.
1684 11672905 Both CTL and antigen-presenting dendritic cells were activated as indicated by a decisive increase in their respective activation markers CD2, CD25, CD28 as well as CD48 and CD80.
1685 11676602 An enhanced and scalable process for the purification of SIV Gag-specific MHC tetramer.
1686 11676602 The purified MHC alpha chain is refolded with beta-2-microglobulin and the target peptide antigen to form the class I MHC.
1687 11676602 An enhanced and scalable process for the purification of SIV Gag-specific MHC tetramer.
1688 11676602 The purified MHC alpha chain is refolded with beta-2-microglobulin and the target peptide antigen to form the class I MHC.
1689 11683578 Both allo and syn fusion cells (FC/MUC1) expressed MHC class II, costimulatory molecules, and the MUC1 antigen.
1690 11684131 PADRE, which binds to several different MHC class II antigen and activates CD4 T cells, induced delayed-type hypersensitivity and stimulated T cell proliferation.
1691 11684131 Therefore, by delivering CD4 and CD8 reactive foreign peptides to the tumor, peptide-specific T cells rejected the tumors as demonstrated by the in vitro and in vivo tests.
1692 11691812 Flow cytometric analysis indicated enhanced expression of MHC class I and II molecules as well as CD80, CD86, CD40, and CD54, and reverse transcription-PCR analysis revealed increased levels of interleukin 12 p40 mRNA.
1693 11691814 Here we describe a novel RCC vaccine strategy that allows for the concomitant delivery of dual immune activators: G250, a widely expressed RCC associated antigen; and granulocyte/macrophage-colony stimulating factor (GM-CSF), an immunomodulatory factor for antigen-presenting cells.
1694 11691814 When combined with interleukin 4 (IL-4; 1000 units/ml), FP (0.34 microg/ml) induces differentiation of monocytes (CD14+) into dendritic cells (DCs) expressing surface markers characteristic for antigen-presenting cells.
1695 11691814 Up-regulation of mature DCs (CD83+CD19-; 17% versus 6%) with enhanced expression of HLA class I and class II antigens was detected in FP-cultured DCs as compared with DCs cultured with recombinant GM-CSF.
1696 11691814 Treatment of peripheral blood mononuclear cells (PBMCs) with FP alone (2.7 microg/10(7) cells) augments both T-cell helper 1 (Th1) and Th2 cytokine mRNA expression (IL-2, IL-4, GM-CSF, IFN-gamma, and tumor necrosis factor-alpha).
1697 11691814 Comparison of various immune manipulation strategies in parallel, bulk PBMCs treated with FP (0.34 microg/ml) plus IL-4 (1000 units/ml) for 1 week and restimulated weekly with FP plus IL-2 (20 IU/ml) induced maximal growth expansion of active T cells expressing the T-cell receptor and specific anti-RCC cytotoxicity, which could be blocked by the addition of anti-HLA class I, anti-CD3, or anti-CD8 antibodies.
1698 11691814 These results suggest that GM-CSF-G250 FP is a potent immunostimulant with the capacity for activating immunomodulatory DCs and inducing a T-helper cell-supported, G250-targeted, and CD8+-mediated antitumor response.
1699 11691814 Here we describe a novel RCC vaccine strategy that allows for the concomitant delivery of dual immune activators: G250, a widely expressed RCC associated antigen; and granulocyte/macrophage-colony stimulating factor (GM-CSF), an immunomodulatory factor for antigen-presenting cells.
1700 11691814 When combined with interleukin 4 (IL-4; 1000 units/ml), FP (0.34 microg/ml) induces differentiation of monocytes (CD14+) into dendritic cells (DCs) expressing surface markers characteristic for antigen-presenting cells.
1701 11691814 Up-regulation of mature DCs (CD83+CD19-; 17% versus 6%) with enhanced expression of HLA class I and class II antigens was detected in FP-cultured DCs as compared with DCs cultured with recombinant GM-CSF.
1702 11691814 Treatment of peripheral blood mononuclear cells (PBMCs) with FP alone (2.7 microg/10(7) cells) augments both T-cell helper 1 (Th1) and Th2 cytokine mRNA expression (IL-2, IL-4, GM-CSF, IFN-gamma, and tumor necrosis factor-alpha).
1703 11691814 Comparison of various immune manipulation strategies in parallel, bulk PBMCs treated with FP (0.34 microg/ml) plus IL-4 (1000 units/ml) for 1 week and restimulated weekly with FP plus IL-2 (20 IU/ml) induced maximal growth expansion of active T cells expressing the T-cell receptor and specific anti-RCC cytotoxicity, which could be blocked by the addition of anti-HLA class I, anti-CD3, or anti-CD8 antibodies.
1704 11691814 These results suggest that GM-CSF-G250 FP is a potent immunostimulant with the capacity for activating immunomodulatory DCs and inducing a T-helper cell-supported, G250-targeted, and CD8+-mediated antitumor response.
1705 11703320 We have analysed the functional capability of DC generated in vitro from blood CD14(+) cells of chronic lymphocytic leukaemia (CLL) patients and healthy donors by culturing for 10 d with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 4 (IL-4) and tumour necrosis factor-alpha (TNF-alpha).
1706 11703320 Most of the DC generated from both patients and controls exhibited a mature phenotype indicated by CD83 and major histocompatibility complex (MHC) class II expression, as well as by a characteristic morphology.
1707 11703320 CLL DC had a similar expression of accessory molecules (CD54, CD80 and CD86) as control DC.
1708 11703320 The mean fluorescence intensity of CD80 and MHC class I molecules was significantly higher on CLL DC than on control DC (P < 0.05).
1709 11703320 The expression of IL-4 and TNF-alpha was similar to that of control DC.
1710 11703320 We have analysed the functional capability of DC generated in vitro from blood CD14(+) cells of chronic lymphocytic leukaemia (CLL) patients and healthy donors by culturing for 10 d with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 4 (IL-4) and tumour necrosis factor-alpha (TNF-alpha).
1711 11703320 Most of the DC generated from both patients and controls exhibited a mature phenotype indicated by CD83 and major histocompatibility complex (MHC) class II expression, as well as by a characteristic morphology.
1712 11703320 CLL DC had a similar expression of accessory molecules (CD54, CD80 and CD86) as control DC.
1713 11703320 The mean fluorescence intensity of CD80 and MHC class I molecules was significantly higher on CLL DC than on control DC (P < 0.05).
1714 11703320 The expression of IL-4 and TNF-alpha was similar to that of control DC.
1715 11705921 Here we have investigated the influence of BCG on the induction of CD1b on human monocytes by granulocyte-macrophage colony-stimulating factor (GM-CSF), which is believed to be the principal inducer of this antigen-presenting molecule.
1716 11705921 Although BCG alone led to a slight induction of CD1b expression, this agent reduced markedly the ability of GM-CSF to induce high levels of CD1b that were typically observed in uninfected cells.
1717 11705921 Down-regulation of CD1b expression by BCG was mediated, at least in part, by one or more soluble factors and could not be reversed with high concentrations of GM-CSF or a variety of other cytokines.
1718 11709777 HLA-A-specific epitopes were predicted from binding motifs, and ELISPOT analyses of patients with DHF revealed high frequencies of circulating CD8 T lymphocytes that recognized both serotype-specific and -cross-reactive dengue virus epitopes.
1719 11709777 Thus, strong CD8 T cell responses are induced by natural dengue virus infection, and HLA class I genetic variation is a risk factor for DHF.
1720 11709777 HLA-A-specific epitopes were predicted from binding motifs, and ELISPOT analyses of patients with DHF revealed high frequencies of circulating CD8 T lymphocytes that recognized both serotype-specific and -cross-reactive dengue virus epitopes.
1721 11709777 Thus, strong CD8 T cell responses are induced by natural dengue virus infection, and HLA class I genetic variation is a risk factor for DHF.
1722 11714768 IL-3 induces B7.2 (CD86) expression and costimulatory activity in human eosinophils.
1723 11714768 IL-5 and GM-CSF induce MHC class II and B7 expression on eosinophils and have been reported in some studies to induce eosinophils to present Ag to T cells.
1724 11714768 The cytokine IL-3, like IL-5 and GM-CSF, is a survival and activating factor for eosinophils and the IL-3 receptor shares with the IL-5 and GM-CSF receptors a common signal transducing beta-chain.
1725 11714768 IL-3-treated eosinophils expressed HLA-DR and B7.2, but not B7.1 on their surface and supported T cell proliferation in response to the superantigen toxic shock syndrome toxin 1, as well as the proliferation of HLA-DR-restricted tetanus toxoid (TT) and influenza hemagglutinin-specific T cell clones to antigenic peptides.
1726 11714768 In parallel experiments, eosinophils treated with IL-5 or GM-CSF were also found to present superantigen and antigenic peptides, but not native Ag, to T cells.
1727 11719435 This epitope was then used to generate de novo human P.polypeptide-specific CD8+ T cells capable of recognizing P.polypeptide expressing human tumor cell lines in an HLA-A*0201-restricted fashion.
1728 11727524 HSPPC-96 is a protein peptide complex consisting of a 96 kDa heat shock protein (Hsp), gp96, and an array of gp96-associated cellular peptides.
1729 11727524 The major mechanism of action is thought to be the ability of HSPPC-96 to prime peptide-specific MHC class I-restricted CD8+ T-cells by interacting with antigen-presenting cells in a receptor-dependent manner.
1730 11730848 C57BL/6 mice were immunized with an adenoviral vector encoding the melanoma antigen gp100 (Ad2/gp100) or were left untreated.
1731 11730848 Blood and spleen cells were restimulated with either a peptide containing the dominant gp100 MHC Class I-restricted epitope, gp100(25-33), or a negative control peptide containing an irrelevant Class I-restricted epitope from ovalbumin.
1732 11745380 The identification of a common pathogen-specific HLA class I A*0201-restricted cytotoxic T cell epitope encoded within the heat shock protein 65.
1733 11745380 Bacterial antigens recognized by CD8(+) T cells in the context of MHC class I are thought to play a crucial role in protection against pathogenic intracellular bacteria.
1734 11745380 Here, we demonstrate the induction of HLA-A*0201-restricted CD8(+) T cell responses against six new high-affinity HLA-A*0201-binding CTL epitopes, encoded within an immunodominant and highly conserved antigen of Mycobacteria, the heat shock protein 65 (hsp65).
1735 11745380 Collectively, these findings describe high-affinity HLA class I-binding epitopes that are naturally processed and are recognized efficiently by MHC class I-restricted CD8(+) T cells, providing a rational basis for the development of subunit vaccine strategies against tuberculosis and other intracellular infectious diseases.
1736 11745380 The identification of a common pathogen-specific HLA class I A*0201-restricted cytotoxic T cell epitope encoded within the heat shock protein 65.
1737 11745380 Bacterial antigens recognized by CD8(+) T cells in the context of MHC class I are thought to play a crucial role in protection against pathogenic intracellular bacteria.
1738 11745380 Here, we demonstrate the induction of HLA-A*0201-restricted CD8(+) T cell responses against six new high-affinity HLA-A*0201-binding CTL epitopes, encoded within an immunodominant and highly conserved antigen of Mycobacteria, the heat shock protein 65 (hsp65).
1739 11745380 Collectively, these findings describe high-affinity HLA class I-binding epitopes that are naturally processed and are recognized efficiently by MHC class I-restricted CD8(+) T cells, providing a rational basis for the development of subunit vaccine strategies against tuberculosis and other intracellular infectious diseases.
1740 11745380 The identification of a common pathogen-specific HLA class I A*0201-restricted cytotoxic T cell epitope encoded within the heat shock protein 65.
1741 11745380 Bacterial antigens recognized by CD8(+) T cells in the context of MHC class I are thought to play a crucial role in protection against pathogenic intracellular bacteria.
1742 11745380 Here, we demonstrate the induction of HLA-A*0201-restricted CD8(+) T cell responses against six new high-affinity HLA-A*0201-binding CTL epitopes, encoded within an immunodominant and highly conserved antigen of Mycobacteria, the heat shock protein 65 (hsp65).
1743 11745380 Collectively, these findings describe high-affinity HLA class I-binding epitopes that are naturally processed and are recognized efficiently by MHC class I-restricted CD8(+) T cells, providing a rational basis for the development of subunit vaccine strategies against tuberculosis and other intracellular infectious diseases.
1744 11745380 The identification of a common pathogen-specific HLA class I A*0201-restricted cytotoxic T cell epitope encoded within the heat shock protein 65.
1745 11745380 Bacterial antigens recognized by CD8(+) T cells in the context of MHC class I are thought to play a crucial role in protection against pathogenic intracellular bacteria.
1746 11745380 Here, we demonstrate the induction of HLA-A*0201-restricted CD8(+) T cell responses against six new high-affinity HLA-A*0201-binding CTL epitopes, encoded within an immunodominant and highly conserved antigen of Mycobacteria, the heat shock protein 65 (hsp65).
1747 11745380 Collectively, these findings describe high-affinity HLA class I-binding epitopes that are naturally processed and are recognized efficiently by MHC class I-restricted CD8(+) T cells, providing a rational basis for the development of subunit vaccine strategies against tuberculosis and other intracellular infectious diseases.
1748 11751972 How H13 histocompatibility peptides differing by a single methyl group and lacking conventional MHC binding anchor motifs determine self-nonself discrimination.
1749 11751972 Moreover, H13 peptides lack the canonical P5(Asn) central anchor residue normally considered important for forming a peptide/MHC complex.
1750 11751972 How H13 histocompatibility peptides differing by a single methyl group and lacking conventional MHC binding anchor motifs determine self-nonself discrimination.
1751 11751972 Moreover, H13 peptides lack the canonical P5(Asn) central anchor residue normally considered important for forming a peptide/MHC complex.
1752 11751984 Generation of genome-wide CD8 T cell responses in HLA-A*0201 transgenic mice by an HIV-1 ubiquitin expression library immunization vaccine.
1753 11751984 These CD8 T cell responses included HLA-A*0201-restricted CTL activity, CD8/IFN-gamma T cell responses, and HLA tetramer binding against defined immunodominant epitopes in gag, pol, env, and nef as well as potent CD8/IFN-gamma responses against undefined HLA-A*0201-restricted epitopes in all remaining Ags of the library.
1754 11751984 Generation of genome-wide CD8 T cell responses in HLA-A*0201 transgenic mice by an HIV-1 ubiquitin expression library immunization vaccine.
1755 11751984 These CD8 T cell responses included HLA-A*0201-restricted CTL activity, CD8/IFN-gamma T cell responses, and HLA tetramer binding against defined immunodominant epitopes in gag, pol, env, and nef as well as potent CD8/IFN-gamma responses against undefined HLA-A*0201-restricted epitopes in all remaining Ags of the library.
1756 11781244 Infection induced DC morphology and altered the expression of surface markers, including loss of CD14, de novo induction of CD83 and CD25, and strongly augmented expression of CD86, CD80, CD40, and HLA-DR and HLA class I molecules.
1757 11782380 NY-ESO-1 119-143 is a promiscuous major histocompatibility complex class II T-helper epitope recognized by Th1- and Th2-type tumor-reactive CD4+ T cells.
1758 11782380 The NY-ESO-1 gene also encodes several MHC class I- and MHC class II-restricted tumor epitopes recognized by T lymphocytes.
1759 11782380 In particular, we previously reported that the NY-ESO-1 119-143 peptide contains at least two HLA-DRB1*0401-presented epitopes that are recognized by melanoma-reactive CD4+ T cells.
1760 11782380 Here we report that the NY-ESO-1 119-143 peptide can be presented in the context of multiple HLA-DR alleles to stimulate tumor-reactive CD4+ T cells.
1761 11782380 The NY-ESO-1 119-143 peptide is also capable of inducing specific CD4+ T cells in vitro from peripheral blood lymphocytes of normal donors and patients with melanoma who express these HLA-DR alleles.
1762 11782380 These CD4+ T cells recognize NY-ESO-1(+), HLA-matched or autologous melanoma cell lines, as well as autologous antigen-presenting cells fed with the NY-ESO-1 protein.
1763 11782380 We also demonstrate that the NY-ESO-1 119-143 peptide stimulates in vitro both Th1-type and Th2-type CD4+ T-cell responses from peripheral blood lymphocytes of normal donors and melanoma patients.
1764 11784213 While past research focused on CD8+ cytotoxic T-cell responses, accumulating evidence suggests that CD4+ T cells also play an important role in orchestrating the host immune response against cancer.
1765 11784213 In this article, we summarise new strategies for the identification of major histocompatibility complex (MHC) class II-associated tumour antigens and discuss the importance of engaging both CD4+ and CD8+ T cells in cancer immunotherapy.
1766 11792386 We selected a panel of 23 8-11 mer Influenza virus (Flu), Cytomegalovirus (CMV) and Epstein Barr virus (EBV) epitopes recognized by CD8 positive T cells and presented by 11 class I HLA-A and HLA-B alleles whose cumulative frequencies represent >100% of Caucasian individuals.
1767 11792386 Release of IFN-gamma in response to the pool of peptides was CD8+ T cell mediated and HLA restricted.
1768 11797392 Formation of tri-molecular complex among T cell antigen receptor(TCR), major histocompatibility complex(MHC) molecule, and antigen peptide produces signal 1 via TCR.
1769 11797392 However, signal 2 is elicited by interaction between CD28 and its ligands(CD80 and CD86) and is antigen-independent.
1770 11797392 Interestingly, cell surface expression of CD80 and CD86 on antigen-presenting cell(APC) is regulated by stimulus via CD40.
1771 11801539 Human T-cell lines generated with the PSA-3A agonist had the ability to lyse human prostate carcinoma cells expressing native PSA in an MHC-restricted manner.
1772 11801539 Recombinant vaccinia viruses were also constructed that contained the entire PSA transgene with and without the single amino acid change that constitutes the PSA-3A epitope; DCs infected with the recombinant vector containing the agonist amino acid change within the entire PSA gene (designated rV-PSA-3A) were more effective than DCs infected with the rV-PSA vector in enhancing IFN-gamma production by T cells.
1773 11807236 We describe 15-mer peptide P8:F92-106 from the F protein of respiratory syncytial virus (RSV) that can act as an MHC class I-restricted (H-2K(d)) epitope for RSV-specific CD8(+) CTL.
1774 11857638 The significance of these observations is discussed within the context of possible mechanisms for the HLA-DM protein that regulates peptide presentation in vivo and the design of non-peptide molecules that can bind MHC II proteins and act as vaccines or immune modulators.
1775 11861381 We distinguished a population of dendrite-like cells among the cells derived from the silica-treated peritoneal cavity both by their phenotype (MHC II(+)/CD80(+)/CD86(+)) and by their ability to induce the proliferation of allogeneic T cells in a mixed leukocyte reaction.
1776 11874634 The immunization protocol consisted of the administration of psoralen-UV-treated and replication-incompetent recombinant vaccinia virus encoding the three immunodominant HLA-A*0201-restricted epitopes Melan-A(27-35), gp100(280-288), and tyrosinase(1-9) together with two costimulatory molecules, B7.1 and B7.2, in the context of systemic granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment.
1777 11895927 The results presented here suggest that costimulatory receptors on CTL such as CD27, CD134 (4-1BB), and MHC class II are capable of directly interacting with the corresponding ligands on T-helper lymphocytes resulting in enhanced proliferation and survival of the CTL during the effector phase of antitumor immune responses.
1778 11896935 Contribution of HLA class I allele expression to CD8+ T-cell responses against Epstein-Barr virus.
1779 11896935 Most immune responses to viral infections involve CD8+ T cells recognizing viral peptides of typically 9-10 amino acids in the groove of major histocompatibility complex (MHC) class I.
1780 11896935 Contribution of HLA class I allele expression to CD8+ T-cell responses against Epstein-Barr virus.
1781 11896935 Most immune responses to viral infections involve CD8+ T cells recognizing viral peptides of typically 9-10 amino acids in the groove of major histocompatibility complex (MHC) class I.
1782 11899255 The role of the ubiquitin-proteasome pathway in MHC class I antigen processing: implications for vaccine design.
1783 11899255 By selective protein degradation, proteasomes regulate many cellular processes including MHC class I antigen processing.
1784 11899255 In this review, we will introduce the ubiquitin-proteasome system and summarize recent findings regarding the role of the IFNgamma-inducible proteasome subunits and proteasome regulators in antigen processing.
1785 11899255 The availability of such programs as well as a general insight into the proteasome mediated steps in MHC class I antigen processing provides us with a rational basis for the design of new antiviral and anticancer T cell vaccines.
1786 11899255 The role of the ubiquitin-proteasome pathway in MHC class I antigen processing: implications for vaccine design.
1787 11899255 By selective protein degradation, proteasomes regulate many cellular processes including MHC class I antigen processing.
1788 11899255 In this review, we will introduce the ubiquitin-proteasome system and summarize recent findings regarding the role of the IFNgamma-inducible proteasome subunits and proteasome regulators in antigen processing.
1789 11899255 The availability of such programs as well as a general insight into the proteasome mediated steps in MHC class I antigen processing provides us with a rational basis for the design of new antiviral and anticancer T cell vaccines.
1790 11899255 The role of the ubiquitin-proteasome pathway in MHC class I antigen processing: implications for vaccine design.
1791 11899255 By selective protein degradation, proteasomes regulate many cellular processes including MHC class I antigen processing.
1792 11899255 In this review, we will introduce the ubiquitin-proteasome system and summarize recent findings regarding the role of the IFNgamma-inducible proteasome subunits and proteasome regulators in antigen processing.
1793 11899255 The availability of such programs as well as a general insight into the proteasome mediated steps in MHC class I antigen processing provides us with a rational basis for the design of new antiviral and anticancer T cell vaccines.
1794 11929777 Increased dendritic cell number and function following continuous in vivo infusion of granulocyte macrophage-colony-stimulating factor and interleukin-4.
1795 11929777 The combination of recombinant granulocyte macrophage-colony-stimulating factor (rGM-CSF) and recombinant interleukin-4 (rIL-4) provides an important stimulus for generating DCs from murine bone marrow precursors in vitro.
1796 11929777 DCs were highly concentrated in the T-cell areas of white pulp after rGM-CSF/IL-4 administration, whereas they were diffusely distributed throughout white pulp, marginal zones, and red pulp in mice treated with rGM-CSF alone. rGM-CSF/rIL-4 also significantly increased the expression of major histocompatibility complex (MHC) class I and MHC class II on CD11c(+) cells and increased their capacity to take up antigens by macropinocytosis and receptor-mediated endocytosis.
1797 11952134 Recently developed single-cell based assays, including peptide major histocompatibility complex (MHC) tetramer staining and intracellular cytokine staining, have greatly enhanced the opportunities for directly studying HCV-specific CD8+ T cells.
1798 11972639 The induced CTL were CD8+, major histocompatibility complex (MHC) class I-restricted and CMV specific.
1799 11992409 We report here on 2 patients who received adjuvant vaccination with an HLA-A2- or HLA-A24-restricted tyrosinase peptide, respectively, and GM-CSF for frequently relapsing stage IV melanoma.
1800 11992409 The T-cell population could be further characterized by 4-color flow cytometry in 1 patient, showing that the majority of the peptide-specific CD3(+)CD8(+)IFN-gamma(+) T cells were granzyme B-positive and CCR-7-negative, characterizing them as effector T cells with the ability to mediate cytotoxicity and migrate to inflamed tissues.
1801 11992409 A single-site postvaccination relapse occurred in both patients, showing downregulation of tyrosinase expression in 1 patient, while normal expression levels for tyrosinase, MHC class I antigens and components of the antigen-processing machinery were found in the other patient.
1802 12006513 The goal of this study was to determine whether HER-2/neu peptide-specific CD8+ T-cell immunity could be elicited using an immunodominant HER-2/neu-derived HLA-A2 peptide alone in the absence of exogenous help.
1803 12006513 Granulocyte macrophage colony-stimulating factor (GM-CSF) was used as adjuvant.
1804 12006513 Six HLA-A2 patients with HER-2/neu-overexpressing cancers received 6 monthly vaccinations with a vaccine preparation consisting of 500 microg of HER-2/neu peptide, p369-377, admixed with 100 microg of GM-CSF.
1805 12006513 These results demonstrate that HER-2/neu MHC class I epitopes can induce HER-2/neu peptide-specific IFN-gamma-producing CD8+ T cells.
1806 12007619 Interferon-gamma (IFN-gamma) production upon specific stimulation by MHC I-restricted peptide was also significantly stronger by the inclusion of LLO in the liposomes.
1807 12021308 There is consensus that an optimized cancer vaccine will have to induce not only CD8+ cytotoxic but also CD4+ T helper (Th) cells, particularly interferon (IFN)-gamma-producing, type 1 Th cells.
1808 12021308 We demonstrate now that the subcutaneous injection of cryopreserved, mature, antigen-loaded, monocyte-derived dendritic cells (DCs) rapidly induces unequivocal Th1 responses (ex vivo detectable IFN-gamma-producing effectors as well as proliferating precursors) both to the control antigen KLH and to major histocompatibility complex (MHC) class II-restricted tumor peptides (melanoma-antigen [Mage]-3.DP4 and Mage-3.DR13) in the majority of 16 evaluable patients with metastatic melanoma.
1809 12021308 These Th1 cells recognized not only peptides, but also DCs loaded with Mage-3 protein, and in case of Mage-3DP4-specific Th1 cells IFN-gamma was released even after direct recognition of viable, Mage-3-expressing HLA-DP4+ melanoma cells.
1810 12023400 We enumerated with HLA-A*0201/peptide tetramers (tHLA) vaccine-elicited CD8(+) T cell precursor frequency among PBMC in 13 patients with melanoma undergoing vaccination with the HLA-A*0201-associated gp100:209-217(210 M) epitope.
1811 12023400 T cell precursor frequency increased from undetectable to 12,400 +/- 3,600 x 10(6) CD8(+) T cells after vaccination and appeared heterogeneous according to previously described functional subtypes: CD45RA(+)CD27(+) (14 +/- 2.6% of tHLA-staining T cells), naive; CD45RA(-)CD27(+) (14 +/- 3.2%), memory; CD45RA(+)CD27(-) (43 +/- 6%), effector; and CD45RA(-)CD27(-) (30 +/- 4.1%), memory/effector.
1812 12023400 The majority of tHLA(+)CD8(+) T cells displayed an effector, CD27(-) phenotype (73%).
1813 12023400 Epitope-specific in vitro stimulation (IVS) followed by 10-day expansion in IL-2 reversed this phenotype by increasing the number of perforin(+) (84 +/- 3.6%; by paired t test, p < 0.001) and CD27(+) (from 28 to 67%; by paired t test, p = 0.01) tHLA(+) T cells.
1814 12033414 Body weight, relative weights of the bursa and the spleen, percentage and relative number of MHC II molecules on MHC II-positive lymphocytes, percentage and relative number of CD4 molecules on CD4-positive lymphocytes, and the specific antibody response all differed significantly among lines.
1815 12039913 The aim of this study is to describe a novel non-live prototype vaccine based on immunopotentiating reconstituted influenza virosomes (IRIV) as vehicles to deliver HLA-A*0201-restricted hepatitis C virus (HCV) peptides (core 35-44 and 131-140) into the cytoplasm of at least three different target cell types [including T2, a transporter associated with antigen processing (TAP)-deficient cell line] resulting in MHC class I peptide presentation and lysis by peptide-specific CTL lines.
1816 12047757 Macrophages showed a rapid inflammatory response in which the expression of interleukin-1beta (IL-1beta), major histocompatibility complex class II (MHC II), inducible cyclo-oxygenase (Cox-2), and inducible nitric oxide synthase (iNOS) was enhanced, but tumour necrosis factor-alpha (TNF-alpha) expression was greatly reduced initially and then increased.
1817 12047757 After 5 days, except for TNF-alpha and MHC II, expression returned to levels approaching those of uninfected macrophages.
1818 12047757 We found that msa reduced the expression of IL-1beta, Cox-2, and MHC II but stimulated TNF-alpha while hly, rsh and grp stimulated MHC II but down-regulated TNF-alpha.
1819 12047757 Constructs expressing hly or lysB stimulated iNOS expression and additionally, lysB stimulated TNF-alpha.
1820 12047757 The results show how p57 suppresses the host immune system and suggest that the immune mechanisms for the containment of R. salmoninarum infections rely on MHC II- and TNF-alpha-dependent pathways.
1821 12047757 Macrophages showed a rapid inflammatory response in which the expression of interleukin-1beta (IL-1beta), major histocompatibility complex class II (MHC II), inducible cyclo-oxygenase (Cox-2), and inducible nitric oxide synthase (iNOS) was enhanced, but tumour necrosis factor-alpha (TNF-alpha) expression was greatly reduced initially and then increased.
1822 12047757 After 5 days, except for TNF-alpha and MHC II, expression returned to levels approaching those of uninfected macrophages.
1823 12047757 We found that msa reduced the expression of IL-1beta, Cox-2, and MHC II but stimulated TNF-alpha while hly, rsh and grp stimulated MHC II but down-regulated TNF-alpha.
1824 12047757 Constructs expressing hly or lysB stimulated iNOS expression and additionally, lysB stimulated TNF-alpha.
1825 12047757 The results show how p57 suppresses the host immune system and suggest that the immune mechanisms for the containment of R. salmoninarum infections rely on MHC II- and TNF-alpha-dependent pathways.
1826 12047757 Macrophages showed a rapid inflammatory response in which the expression of interleukin-1beta (IL-1beta), major histocompatibility complex class II (MHC II), inducible cyclo-oxygenase (Cox-2), and inducible nitric oxide synthase (iNOS) was enhanced, but tumour necrosis factor-alpha (TNF-alpha) expression was greatly reduced initially and then increased.
1827 12047757 After 5 days, except for TNF-alpha and MHC II, expression returned to levels approaching those of uninfected macrophages.
1828 12047757 We found that msa reduced the expression of IL-1beta, Cox-2, and MHC II but stimulated TNF-alpha while hly, rsh and grp stimulated MHC II but down-regulated TNF-alpha.
1829 12047757 Constructs expressing hly or lysB stimulated iNOS expression and additionally, lysB stimulated TNF-alpha.
1830 12047757 The results show how p57 suppresses the host immune system and suggest that the immune mechanisms for the containment of R. salmoninarum infections rely on MHC II- and TNF-alpha-dependent pathways.
1831 12047757 Macrophages showed a rapid inflammatory response in which the expression of interleukin-1beta (IL-1beta), major histocompatibility complex class II (MHC II), inducible cyclo-oxygenase (Cox-2), and inducible nitric oxide synthase (iNOS) was enhanced, but tumour necrosis factor-alpha (TNF-alpha) expression was greatly reduced initially and then increased.
1832 12047757 After 5 days, except for TNF-alpha and MHC II, expression returned to levels approaching those of uninfected macrophages.
1833 12047757 We found that msa reduced the expression of IL-1beta, Cox-2, and MHC II but stimulated TNF-alpha while hly, rsh and grp stimulated MHC II but down-regulated TNF-alpha.
1834 12047757 Constructs expressing hly or lysB stimulated iNOS expression and additionally, lysB stimulated TNF-alpha.
1835 12047757 The results show how p57 suppresses the host immune system and suggest that the immune mechanisms for the containment of R. salmoninarum infections rely on MHC II- and TNF-alpha-dependent pathways.
1836 12057610 To study whether SIV VLPs represent effective mucosal immunogens, we immunized groups of mice with VLPs alone or VLPs plus the mucosal adjuvant cholera toxin (CT) by the intranasal (i.n.) route.
1837 12057610 High levels of serum IgG antibody production were achieved in mice immunized intranasally with SIV VLPs, and the antibody response was found to be antigen dose-dependent.
1838 12057610 The IgG1 and IgG2a ratio indicates that immune responses induced by SIV VLPs are Th1 oriented.
1839 12057610 Moreover, increased numbers of MHC I-restricted peptide-specific IFN-gamma and IL-4 producing T cells were detected in both splenocytes and lymph nodes by intranasal immunization of SIV VLP plus CT.
1840 12067417 We evaluated three unrelated computational methods to screen Pol, Gag and Env sequences extracted from the Los Alamos HIV database for HLA-A*0201 and HLA-B*3501 T-cell epitope candidates.
1841 12069379 The cytokine used most extensively to date is interleukin-2 (IL2), a molecule that induces T lymphocyte proliferation and the generation of MHC unrestricted cytotoxicity.
1842 12072267 Candidate vaccine antigens for cellular immune responses should therefore be analysed in the context of MHC class I antigen presentation.
1843 12072268 Broiler sire alleles of the MHC class I, NRAMP1, PSAP, and IAP1 genes showed association with SE colonization in the F(1) generation of this novel disease resistance resource population.
1844 12077290 Generation of CTL recognizing an HLA-A*0201-restricted epitope shared by MAGE-A1, -A2, -A3, -A4, -A6, -A10, and -A12 tumor antigens: implication in a broad-spectrum tumor immunotherapy.
1845 12077290 MAGE-A1, -A2, -A3, -A4, -A6, -A10, and -A12 are expressed in a significant proportion of primary and metastatic tumors of various histological types and are targets of tumor Ag-specific CTL.
1846 12077290 These CTL are able to recognize two low HLA-A*0201 affinity peptides differing at their C-terminal position and derived from MAGE-A2, -A3, -A4, -A6, -A10, and -A12 (p248G9) and MAGE-A1 (p248D9).
1847 12077290 Interestingly, p248V9-specific CTL respond to endogenous MAGE-A1, -A2, -A3, -A4, -A6, -A10, and -A12 in an HLA-A*0201-restricted manner and recognize human HLA-A*0201(+)MAGE-A(+) tumor cells of various histological origin.
1848 12077290 Generation of CTL recognizing an HLA-A*0201-restricted epitope shared by MAGE-A1, -A2, -A3, -A4, -A6, -A10, and -A12 tumor antigens: implication in a broad-spectrum tumor immunotherapy.
1849 12077290 MAGE-A1, -A2, -A3, -A4, -A6, -A10, and -A12 are expressed in a significant proportion of primary and metastatic tumors of various histological types and are targets of tumor Ag-specific CTL.
1850 12077290 These CTL are able to recognize two low HLA-A*0201 affinity peptides differing at their C-terminal position and derived from MAGE-A2, -A3, -A4, -A6, -A10, and -A12 (p248G9) and MAGE-A1 (p248D9).
1851 12077290 Interestingly, p248V9-specific CTL respond to endogenous MAGE-A1, -A2, -A3, -A4, -A6, -A10, and -A12 in an HLA-A*0201-restricted manner and recognize human HLA-A*0201(+)MAGE-A(+) tumor cells of various histological origin.
1852 12077290 Generation of CTL recognizing an HLA-A*0201-restricted epitope shared by MAGE-A1, -A2, -A3, -A4, -A6, -A10, and -A12 tumor antigens: implication in a broad-spectrum tumor immunotherapy.
1853 12077290 MAGE-A1, -A2, -A3, -A4, -A6, -A10, and -A12 are expressed in a significant proportion of primary and metastatic tumors of various histological types and are targets of tumor Ag-specific CTL.
1854 12077290 These CTL are able to recognize two low HLA-A*0201 affinity peptides differing at their C-terminal position and derived from MAGE-A2, -A3, -A4, -A6, -A10, and -A12 (p248G9) and MAGE-A1 (p248D9).
1855 12077290 Interestingly, p248V9-specific CTL respond to endogenous MAGE-A1, -A2, -A3, -A4, -A6, -A10, and -A12 in an HLA-A*0201-restricted manner and recognize human HLA-A*0201(+)MAGE-A(+) tumor cells of various histological origin.
1856 12078650 In this study, we analysed HLA-A*0201 specific CD8(-) T-lymphocyte responses to the P. vivax circumsporozoite (CS) protein in both malaria exposed and non-exposed populations from the Colombian Pacific Coast.
1857 12078650 We then selected, on the P. vivax CS, five peptide sequences containing the HLA-A*0201 binding motifs and used the corresponding synthetic peptides to evaluate the CD8(-) T-lymphocyte interferon (IFN)-gamma response.
1858 12078650 Peripheral blood mononuclear cells from the HLA-A*0201 donors were in vitro stimulated with these peptides and IFN-gamma production was determined by an ELISPOT assay.
1859 12078650 In this study, we analysed HLA-A*0201 specific CD8(-) T-lymphocyte responses to the P. vivax circumsporozoite (CS) protein in both malaria exposed and non-exposed populations from the Colombian Pacific Coast.
1860 12078650 We then selected, on the P. vivax CS, five peptide sequences containing the HLA-A*0201 binding motifs and used the corresponding synthetic peptides to evaluate the CD8(-) T-lymphocyte interferon (IFN)-gamma response.
1861 12078650 Peripheral blood mononuclear cells from the HLA-A*0201 donors were in vitro stimulated with these peptides and IFN-gamma production was determined by an ELISPOT assay.
1862 12078650 In this study, we analysed HLA-A*0201 specific CD8(-) T-lymphocyte responses to the P. vivax circumsporozoite (CS) protein in both malaria exposed and non-exposed populations from the Colombian Pacific Coast.
1863 12078650 We then selected, on the P. vivax CS, five peptide sequences containing the HLA-A*0201 binding motifs and used the corresponding synthetic peptides to evaluate the CD8(-) T-lymphocyte interferon (IFN)-gamma response.
1864 12078650 Peripheral blood mononuclear cells from the HLA-A*0201 donors were in vitro stimulated with these peptides and IFN-gamma production was determined by an ELISPOT assay.
1865 12080377 Peptides derived from the wild-type (wt) p53 protein and presented by major histocompatibility complex (MHC) molecules for T lymphocyte recognition are believed to serve as universal tumor-associated antigens for cancer immunotherapy.
1866 12080377 However, p53-reactive antibodies and HLA-A*0201 (A2.1)-restricted CTLs specific for wt p53 epitopes were not generated.
1867 12080377 Peptides derived from the wild-type (wt) p53 protein and presented by major histocompatibility complex (MHC) molecules for T lymphocyte recognition are believed to serve as universal tumor-associated antigens for cancer immunotherapy.
1868 12080377 However, p53-reactive antibodies and HLA-A*0201 (A2.1)-restricted CTLs specific for wt p53 epitopes were not generated.
1869 12085321 This study examined the biologic responses of transgenic mice expressing human leukocyte antigen (HLA)-DR3 and human CD4 molecules, in the absence of murine major histocompatibility complex (MHC) class II molecules (Ab(0)), to staphylococcal enterotoxins (SEs) and evaluated protective immunity of a nonsuperantigen form of SEB against wild-type holotoxin.
1870 12093890 Here we show that targeting of antigen to Fc receptors on DCs accomplishes combined activation of Th1 CD4 and CD8 effector responses in vivo, namely delayed-type hypersensitivity and tumor immunity.
1871 12093890 Tumor protection was eliminated when immune complex-loaded DCs lacked beta(2) microglobulin, TAP, or MHC class II, demonstrating that Fc receptor-targeted antigenic uptake led to both MHC class I- and class II-restricted responses, which together are required for effector tumor immunity.
1872 12095169 The partial ECD sequence of HER2/neu includes five rat major histocompatibility (MHC)-II-restricted peptides with complete human-to-rat cross-species homology.
1873 12095169 Both vaccines induced HER2/neu-specific antibody titers.
1874 12095169 Our data suggests that the HER2/neu-EGFP-MatLyLu tumor is a potential animal tumor model for investigating therapeutic vaccine strategies against PC in vivo and demonstrates the limitations of a cDNA vaccine only encoding for MHC-II-restricted HER2/neu-ECD sequence peptides.
1875 12095169 The partial ECD sequence of HER2/neu includes five rat major histocompatibility (MHC)-II-restricted peptides with complete human-to-rat cross-species homology.
1876 12095169 Both vaccines induced HER2/neu-specific antibody titers.
1877 12095169 Our data suggests that the HER2/neu-EGFP-MatLyLu tumor is a potential animal tumor model for investigating therapeutic vaccine strategies against PC in vivo and demonstrates the limitations of a cDNA vaccine only encoding for MHC-II-restricted HER2/neu-ECD sequence peptides.
1878 12098604 Thus, we have attempted to identify MHC class II-restricted tumor antigens recognized by tumor-specific CD4+ T cells.
1879 12111121 Molecular requirements for CD8-mediated rejection of a MUC1-expressing pancreatic carcinoma: implications for tumor vaccines.
1880 12111121 We confirmed that a CD8(+) effector cell was required to eliminate MUC1-expressing Panc02 tumors, and demonstrated that T cells expressing TCR-alpha/beta and co-stimulation through CD28 and CD40:CD40L interactions played critical roles during the initiation of the anti-Panc02.MUC1 immune response.
1881 12111121 TCR-alpha/beta(+) cells were required to eliminate Panc02.MUC1 tumors, while TCR-gamma/delta(+) cells played a suppressive non-MUC1-specific role in anti-Panc02 tumor immunity.
1882 12111121 Type 1 cytokine interferon-gamma (IFN-gamma), but not interleukin-12 (IL-12), was essential for eliminating MUC1-expressing tumors, while neither IL-4 nor IL-10 (type 2 cytokines) were required for tumor rejection.
1883 12111121 In vitro studies demonstrated that IFN-gamma upregulated MHC class I, but not MHC class II, on Panc02.MUC1 tumor cells.
1884 12111121 Surprisingly, both perforin and FasL played unique roles during the effector phase of immunity to Panc02.MUC1, while lymphotoxin-alpha, but not TNFR-1, was required for immunity against Panc02.MUC1 tumors.
1885 12111122 We showed that bone marrow-derived DC pulsed with Id-CD40L upregulated the expression of CD40, CD80, CD86, and major histocompatibility complex (MHC) class II molecules with the increased production of interleukin-12 (IL-12).
1886 12112675 A three-dimensional quantitative structure-activity relationship method for the prediction of peptide binding affinities to the MHC class I molecule HLA-A*0201 was developed by applying the CoMSIA technique on a set of 266 peptides.
1887 12115646 To establish a new immunotherapy for type I allergic diseases without allergic side effects, we attempted to develop a DNA vaccine encoding both a CD4+ T cell epitope site in a major Japanese cedar pollen allergen (Cry j 2) and an invariant chain (Ii) for the delivery of the epitope peptide into the MHC class II loading pathway.
1888 12117906 CTL activity was observed in sorted alphabeta+ CD8+ T cells, which were remarkably increased after expansion, but not in CD4+ T cells.
1889 12117906 This is the first demonstration that Salmonella serovar Typhi vaccines delivered intranasally elicit CD8+ MHC class I-restricted CTL.
1890 12130509 In this study, we determined the ability to generate Sp17-specific HLA class I-restricted cytotoxic T lymphocytes (CTLs) from the peripheral blood of 4 patients with MM, 3 consecutive Sp17(+) patients, and 1 Sp17(-) patient.
1891 12133998 Novel role of CD8(+) T cells and major histocompatibility complex class I genes in the generation of protective CD4(+) Th1 responses during retrovirus infection in mice.
1892 12133998 CD4(+) Th1 responses to virus infections are often necessary for the development and maintenance of virus-specific CD8(+) T-cell responses.
1893 12133998 In the absence of a responder H-2(b) allele at major histocompatibility complex (MHC) class II loci, a single H-2D(b) MHC class I allele was sufficient for the development of a CD4(+) Th1 response to FV.
1894 12133998 This effect of H-2D(b) on CD4(+) T-cell responses was dependent on CD8(+) T cells, as demonstrated by depletion studies.
1895 12133998 A direct effect of CD8(+) T-cell help in the development of CD4(+) Th1 responses to FV was also shown in vaccine studies.
1896 12133998 Adoptive transfer of vaccine-primed CD8(+) T cells to naive H-2(a/a) mice prior to infection resulted in the generation of FV-specific CD4(+) Th1 responses.
1897 12133998 This novel helper effect of CD8(+) T cells could be an important mechanism in the development of CD4(+) Th1 responses following vaccinations that induce CD8(+) CTL responses.
1898 12133998 The ability of MHC class I genes to facilitate CD4(+) Th1 development could also be considerable evolutionary advantage by allowing a wider variety of MHC genotypes to generate protective immune responses against intracellular pathogens.
1899 12133998 Novel role of CD8(+) T cells and major histocompatibility complex class I genes in the generation of protective CD4(+) Th1 responses during retrovirus infection in mice.
1900 12133998 CD4(+) Th1 responses to virus infections are often necessary for the development and maintenance of virus-specific CD8(+) T-cell responses.
1901 12133998 In the absence of a responder H-2(b) allele at major histocompatibility complex (MHC) class II loci, a single H-2D(b) MHC class I allele was sufficient for the development of a CD4(+) Th1 response to FV.
1902 12133998 This effect of H-2D(b) on CD4(+) T-cell responses was dependent on CD8(+) T cells, as demonstrated by depletion studies.
1903 12133998 A direct effect of CD8(+) T-cell help in the development of CD4(+) Th1 responses to FV was also shown in vaccine studies.
1904 12133998 Adoptive transfer of vaccine-primed CD8(+) T cells to naive H-2(a/a) mice prior to infection resulted in the generation of FV-specific CD4(+) Th1 responses.
1905 12133998 This novel helper effect of CD8(+) T cells could be an important mechanism in the development of CD4(+) Th1 responses following vaccinations that induce CD8(+) CTL responses.
1906 12133998 The ability of MHC class I genes to facilitate CD4(+) Th1 development could also be considerable evolutionary advantage by allowing a wider variety of MHC genotypes to generate protective immune responses against intracellular pathogens.
1907 12149420 Although BRSV did not appear to replicate in MoDC or to affect expression of major histocompatibility complex (MHC) class I, MHC class II, or CD80/86, a higher percentage of cells exposed to live virus appeared to undergo apoptosis/necrosis.
1908 12149420 Exposure of MoDC to live BRSV induced more interleukin (IL)-10 mRNA and markedly less IL-12p40 and IL-15 mRNA than did heat-inactivated virus.
1909 12149420 Stimulation of CD4(+) T cells induced similar levels of IL-2-and IL-4-like activity and interferon-gamma.
1910 12149420 These observations suggest that while IL-10, produced by MoDC as a result of exposure to live BRSV, may affect IL-12 and IL-15 synthesis by MoDC, it does not appear to affect the cytokine response of BRSV-specific memory CD4(+) T cells.
1911 12163589 HIV-1-specific CD8+ T-cell responses broadened significantly during subsequent exposure to the virus, ultimately targeting 27 distinct CTL epitopes, including 15 different CTL epitopes restricted by a single HLA class I allele (HLA-A3).
1912 12165513 T cell recognition of an engineered MHC class I molecule: implications for peptide-independent alloreactivity.
1913 12165513 Previously, we described H-2K(bW9) (K(bW9)), an engineered variant of the murine MHC class I molecule H-2K(b) (K(b)), devoid of the central anchor ("C") pocket owing to a point mutation on the floor of the peptide binding site; this substitution drastically altered selection of bound peptides, such that the peptide repertoires of K(b) and K(bW9) are largely nonoverlapping in vivo.
1914 12165513 T cell recognition of an engineered MHC class I molecule: implications for peptide-independent alloreactivity.
1915 12165513 Previously, we described H-2K(bW9) (K(bW9)), an engineered variant of the murine MHC class I molecule H-2K(b) (K(b)), devoid of the central anchor ("C") pocket owing to a point mutation on the floor of the peptide binding site; this substitution drastically altered selection of bound peptides, such that the peptide repertoires of K(b) and K(bW9) are largely nonoverlapping in vivo.
1916 12165547 Inhibition of EBV-induced lymphoproliferation by CD4(+) T cells specific for an MHC class II promiscuous epitope.
1917 12182454 Depletion of either CD4+ T cells, CD8+ T cells or CD16+/CD56+ T cells by immunomagnetic separation demonstrated that TT-specific IFN-gamma secretion is mediated exclusively by CD4+ T cells.
1918 12182454 In addition, HLA class-I and -II blocking studies showed that IFN-gamma production is performed by HLA class-II restricted cells.
1919 12182454 Our data show that the Elispot assay can be reliably used to assess the number of TT-specific CD4+ IFN-gamma producing cells (i.e. probably T helper cells) and therefore maybe also useful for the assessment of reactions to other helper antigens.
1920 12189248 Using human leukocyte antigen (HLA) class I tetramers, we observed that HSV-specific CD8(+) T cells in the peripheral blood expressed high levels of cutaneous lymphocyte-associated antigen (CLA).
1921 12189248 In contrast, CD8(+) T cells specific for non-skin-tropic herpesviruses lacked CLA expression.
1922 12189248 CLA-positive HSV-2-specific CD8(+) T cells had the characteristics of central memory cells, expressing CCR7, CD62L, and CD28, and they proliferated briskly in response to antigen.
1923 12189248 A higher proportion of HSV-specific CD8(+) T cells recovered from herpes lesions express CLA compared with blood, consistent with a role for CLA in skin homing.
1924 12195377 This study used a transgenic murine model expressing human major histocompatibility complex (MHC) class II and human CD4 in which, without additional toxic sensitization, human-like responses to the bacterial superantigen (SAg) streptococcal pyrogenic exotoxin A (SpeA) could be simulated, as determined by studying multiple biologic effects of the SAgs in vivo.
1925 12218775 This study uses four-color flow cytometry to show that HLA-A*0201-tHLA-stained CD8(-) cells can be divided into two subsets: 87% represent B-lymphocytes (CD19(+), CD45RA(+), HLA-DR(+), and CD20(+)), and 13% represent T-helper cells (CD3(+), CD4(+), CD45RA(+), and CD27(+)).
1926 12228278 The present study was designed to identify conserved CD4(+) T-cell epitopes in MSP1a presented by a broadly represented subset of major histocompatibility complex (MHC) class II molecules that would be suitable for inclusion in a recombinant vaccine.
1927 12231526 Identification of a novel HLA-A*0201-restricted, cytotoxic T lymphocyte epitope in a human glioma-associated antigen, interleukin 13 receptor alpha2 chain.
1928 12244180 DNA-encoded fetal liver tyrosine kinase 3 ligand and granulocyte macrophage-colony-stimulating factor increase dendritic cell recruitment to the inoculation site and enhance antigen-specific CD4+ T cell responses induced by DNA vaccination of outbred animals.
1929 12244180 The second hypothesis, that DNA encoding Flt3L and GM-CSF enhances immunity to a DNA vector-expressed Ag, was tested by analyzing the CD4(+) T lymphocyte response to Anaplasma marginale major surface protein 1a (MSP1a).
1930 12244180 Calves immunized with DNA-expressing MSP1a developed strong CD4(+) T cell responses against A. marginale, MSP1a, and specific MHC class II DR-restricted MSP1a epitopes.
1931 12244180 Administration of DNA-encoding Flt3L and GM-CSF before MSP1a DNA vaccination significantly increased the population of Ag-specific effector/memory cells in PBMC and significantly enhanced MSP1a-specific CD4(+) T cell proliferation and IFN-gamma secretion as compared with MHC class II DR-matched calves vaccinated identically but without Flt3L and GM-CSF.
1932 12244180 DNA-encoded fetal liver tyrosine kinase 3 ligand and granulocyte macrophage-colony-stimulating factor increase dendritic cell recruitment to the inoculation site and enhance antigen-specific CD4+ T cell responses induced by DNA vaccination of outbred animals.
1933 12244180 The second hypothesis, that DNA encoding Flt3L and GM-CSF enhances immunity to a DNA vector-expressed Ag, was tested by analyzing the CD4(+) T lymphocyte response to Anaplasma marginale major surface protein 1a (MSP1a).
1934 12244180 Calves immunized with DNA-expressing MSP1a developed strong CD4(+) T cell responses against A. marginale, MSP1a, and specific MHC class II DR-restricted MSP1a epitopes.
1935 12244180 Administration of DNA-encoding Flt3L and GM-CSF before MSP1a DNA vaccination significantly increased the population of Ag-specific effector/memory cells in PBMC and significantly enhanced MSP1a-specific CD4(+) T cell proliferation and IFN-gamma secretion as compared with MHC class II DR-matched calves vaccinated identically but without Flt3L and GM-CSF.
1936 12297327 Immune evasion by a novel family of viral PHD/LAP-finger proteins of gamma-2 herpesviruses and poxviruses.
1937 12297327 Recent observations however, suggest that a conserved family of viral proteins is used by both gamma-2 herpesviruses and by poxviruses to downregulate MHC class I.
1938 12379326 These particles contain antigen presenting molecules (MHC class I, MHC class II, and CD1), tetraspan molecules (CD9, CD63, CD81), adhesion molecules (CD11b and CD54), and costimulatory molecules (CD86); hence, providing them the necessary machinery required for generating a potent immune response [J.
1939 12388723 The simian immunodeficiency virus (SIV)-infected rhesus macaque is the best available animal model for AIDS, but analysis of macaque CTL responses has hitherto focused mainly on epitopes bound by a single major histocompatibility complex (MHC) class I molecule, Mamu-A*01.
1940 12388723 Both epitopes are bound by the common macaque MHC class I molecule, Mamu-A*02.
1941 12388723 The simian immunodeficiency virus (SIV)-infected rhesus macaque is the best available animal model for AIDS, but analysis of macaque CTL responses has hitherto focused mainly on epitopes bound by a single major histocompatibility complex (MHC) class I molecule, Mamu-A*01.
1942 12388723 Both epitopes are bound by the common macaque MHC class I molecule, Mamu-A*02.
1943 12391194 High-affinity HLA-A(*)02.01 peptides from parathyroid hormone-related protein generate in vitro and in vivo antitumor CTL response without autoimmune side effects.
1944 12391194 Parathyroid hormone-related protein (PTH-rP), a protein produced by prostate carcinoma and other epithelial cancers, is a key agent in the development of bone metastases.
1945 12391194 We investigated whether the protein follows the self-tolerance paradigm or can be used as a target Ag for anticancer immunotherapy by investigating the immunogenicity of two HLA-A(*)02.01-binding PTH-rP-derived peptides (PTR-2 and -4) with different affinity qualities.
1946 12391194 PTH-rP peptide-specific CTL lines were generated from the PBMC of two HLA-A(*)02.01(+) healthy individuals, stimulated in vitro with PTH-rP peptide-loaded autologous dendritic cells and IL-2.
1947 12391194 High-affinity HLA-A(*)02.01 peptides from parathyroid hormone-related protein generate in vitro and in vivo antitumor CTL response without autoimmune side effects.
1948 12391194 Parathyroid hormone-related protein (PTH-rP), a protein produced by prostate carcinoma and other epithelial cancers, is a key agent in the development of bone metastases.
1949 12391194 We investigated whether the protein follows the self-tolerance paradigm or can be used as a target Ag for anticancer immunotherapy by investigating the immunogenicity of two HLA-A(*)02.01-binding PTH-rP-derived peptides (PTR-2 and -4) with different affinity qualities.
1950 12391194 PTH-rP peptide-specific CTL lines were generated from the PBMC of two HLA-A(*)02.01(+) healthy individuals, stimulated in vitro with PTH-rP peptide-loaded autologous dendritic cells and IL-2.
1951 12391194 High-affinity HLA-A(*)02.01 peptides from parathyroid hormone-related protein generate in vitro and in vivo antitumor CTL response without autoimmune side effects.
1952 12391194 Parathyroid hormone-related protein (PTH-rP), a protein produced by prostate carcinoma and other epithelial cancers, is a key agent in the development of bone metastases.
1953 12391194 We investigated whether the protein follows the self-tolerance paradigm or can be used as a target Ag for anticancer immunotherapy by investigating the immunogenicity of two HLA-A(*)02.01-binding PTH-rP-derived peptides (PTR-2 and -4) with different affinity qualities.
1954 12391194 PTH-rP peptide-specific CTL lines were generated from the PBMC of two HLA-A(*)02.01(+) healthy individuals, stimulated in vitro with PTH-rP peptide-loaded autologous dendritic cells and IL-2.
1955 12391201 CD28, TNF receptor, and IL-12 are critical for CD4-independent cross-priming of therapeutic antitumor CD8+ T cells.
1956 12391201 Previously, we have shown that priming of therapeutic CD8(+) T cells in tumor vaccine-draining lymph nodes of mice vaccinated with GM-CSF secreting B16BL6 melanoma cells occurs independent of CD4 T cell help.
1957 12391201 In this study, we examined the contribution of the major costimulatory molecules, CD40 ligand (CD40L), CD80, and CD86, in the priming of CD8(+) T cells.
1958 12391201 Priming of therapeutic CD8(+) T cells by a GM-CSF-transduced tumor vaccine did not require CD40 and CD40L interactions, as therapeutic T cells could be generated from mice injected with anti-CD40L Ab and from CD40L knockout mice.
1959 12391201 However, costimulation via either CD80 or CD86 was required, as therapeutic T cells could be generated from mice injected with either anti-CD80 or anti-CD86 Ab alone, but administration of both Abs completely inhibited the priming of therapeutic T cells.
1960 12391201 Blocking experiments also identified that priming of therapeutic T cells in MHC class II-deficient mice required TNFR and IL-12 signaling, but signaling through CD40, lymphotoxin-betaR, or receptor activator of NF-kappaB was not essential.
1961 12391201 Thus, cross-priming of therapeutic CD8(+) T cells by a tumor vaccine transduced with GM-CSF requires TNFR, IL-12, and CD28 signaling.
1962 12393660 Autologous and MHC class I-negative allogeneic tumor cells secreting IL-12 together cure disseminated A20 lymphoma.
1963 12393660 Here, we show that allogeneic B78H1 major histocompatibility complex (MHC) class I-negative and -positive (H-2K(b)- and D(b)-transfected) cells induced cytotoxic T lymphocytes (CTLs) and protection in BALB/c mice at comparable levels in response to a challenge with C26 (H-2(d)) colon carcinoma cells sharing the tumor-associated antigen envelope glycoprotein 70 (env-gp70) with both cell lines.
1964 12393660 Indeed, only CD4(+) T cells from IL-12-treated mice could be restimulated with anti-OX40 monoclonal antibody (mAb) in place of a fourth cellular boost.
1965 12393660 Moreover, the IL-12-based tumor vaccine induced expansion of tumor-specific interferon-gamma (IFN-gamma)-producing CD8(+) T cells.
1966 12393660 Autologous and MHC class I-negative allogeneic tumor cells secreting IL-12 together cure disseminated A20 lymphoma.
1967 12393660 Here, we show that allogeneic B78H1 major histocompatibility complex (MHC) class I-negative and -positive (H-2K(b)- and D(b)-transfected) cells induced cytotoxic T lymphocytes (CTLs) and protection in BALB/c mice at comparable levels in response to a challenge with C26 (H-2(d)) colon carcinoma cells sharing the tumor-associated antigen envelope glycoprotein 70 (env-gp70) with both cell lines.
1968 12393660 Indeed, only CD4(+) T cells from IL-12-treated mice could be restimulated with anti-OX40 monoclonal antibody (mAb) in place of a fourth cellular boost.
1969 12393660 Moreover, the IL-12-based tumor vaccine induced expansion of tumor-specific interferon-gamma (IFN-gamma)-producing CD8(+) T cells.
1970 12393675 Identification of immunodominant regions among promiscuous HLA-DR-restricted CD4+ T-cell epitopes on the tumor antigen MAGE-3.
1971 12393675 We used a major histocompatability complex (MHC) class II epitope prediction algorithm, the TEPITOPE software, to predict 11 sequence segments of MAGE-3 that could form promiscuous CD4(+) T-cell epitopes.
1972 12393675 The immunodominant epitopes identified will be useful in the design of peptide-based cancer vaccines and in the study of the functional state of tumor-specific CD4(+) T cells in patients bearing tumors expressing MAGE-3.
1973 12396610 HLA class I restriction and cytotoxic activity were confirmed after isolation of peptide-specific CD8+ T-cell lines.
1974 12399202 CD4+ and CD8+ mediated cellular immune response to recombinant influenza nucleoprotein.
1975 12399202 The stimulatory properties of soluble recombinant influenza nucleoprotein (NP) on purified CD4(+) and CD8(+) T cells from young and elderly individuals were studied.
1976 12399202 Recombinant influenza NP failed to induce proliferation of resting CD4(+) and CD8(+) T cells in the absence of IL-2.
1977 12399202 Addition of small amounts of IL-2, however, led to strong proliferation of resting CD4(+) and CD8(+) T cells from young and elderly donors.
1978 12399202 NP-reactive CD4(+) and CD8(+) T cell lines from both age groups grew equally well under long-term culture conditions.
1979 12399202 Stimulation of CD8(+) T cells is presumably due to cross-presentation, as EBV-transformed MHC class I-positive cell lines, which are incapable of antigen processing, stimulated live influenza virus-reactive CD8(+) T cell lines when loaded with NP-derived immunodominant peptides but not following loading with the whole NP molecule.
1980 12399204 The ability of bovine herpesvirus-1 (BHV-1) to undergo latency, to induce apoptosis of CD4(+) T-lymphocytes, and to down-regulate the expression of major histocompatibility complex (MHC) class I molecules, necessitates the development of immunization strategies that do not involve the live virus.
1981 12402309 Prostate stem cell antigen: Identification of immunogenic peptides and assessment of reactive CD8+ T cells in prostate cancer patients.
1982 12402309 In this report, we define immunogenic peptides of PSCA which are recognized by circulating CD8(+) T cells from prostate cancer patients and able to activate CTLs in vitro.
1983 12402309 Screening the amino acid sequence of PSCA for peptides containing a binding motif for HLA-A*0201 resulted in 8 candidate peptides.
1984 12402309 They specifically recognized peptide-pulsed T2 target cells and prostate cancer cells that were HLA-A*0201- and PSCA-positive, indicating that these peptides were naturally generated by tumor cells.
1985 12402309 Prostate stem cell antigen: Identification of immunogenic peptides and assessment of reactive CD8+ T cells in prostate cancer patients.
1986 12402309 In this report, we define immunogenic peptides of PSCA which are recognized by circulating CD8(+) T cells from prostate cancer patients and able to activate CTLs in vitro.
1987 12402309 Screening the amino acid sequence of PSCA for peptides containing a binding motif for HLA-A*0201 resulted in 8 candidate peptides.
1988 12402309 They specifically recognized peptide-pulsed T2 target cells and prostate cancer cells that were HLA-A*0201- and PSCA-positive, indicating that these peptides were naturally generated by tumor cells.
1989 12407427 Efficient transduction and long-term retroviral expression of the melanoma-associated tumor antigen tyrosinase in CD34(+) cord blood-derived dendritic cells.
1990 12407427 To prove this, we utilized a retroviral vector with bicistronic expression of the melanoma-associated antigen tyrosinase and the enhanced green fluorescent protein (EGFP).
1991 12407427 Intracellular processing of the provirally expressed tyrosinase was tested in a chromium release assay utilizing a cytotoxic T cell clone specific for a HLA-A*0201-restricted tyrosinase peptide.
1992 12433366 We show that this peptide is remarkably immunodominant in that it competes effectively with MHC alloantigens, is efficiently crosspresented by host antigen-presenting cells (APCs), and readily elicits naive CD8 T cell responses in vitro.
1993 12439621 Alleles defined by a Lys(148)-->Met(148) polymorphism in the MHC class I alpha(2) domain were associated with spleen bacterial load after SE challenge.
1994 12445282 However, recent studies suggest that therapeutic strategies that have mainly focused on the use of CD8+ T cells (and MHC class I-restricted tumor antigens) may not be effective in eliminating cancer cells in patients.
1995 12445282 Novel strategies have been developed for enhancing T-cell responses against cancer by prolonging antigen presentation of dendritic cells to T cells and the inclusion of MHC class II-restricted tumor antigens. identification of MHC class II-restricted tumor antigens, which are capable of stimulating CD4+ T cells, not only aids our understanding of the host immune responses against cancer antigens, but also provides opportunities for developing effective cancer vaccines.
1996 12445282 However, recent studies suggest that therapeutic strategies that have mainly focused on the use of CD8+ T cells (and MHC class I-restricted tumor antigens) may not be effective in eliminating cancer cells in patients.
1997 12445282 Novel strategies have been developed for enhancing T-cell responses against cancer by prolonging antigen presentation of dendritic cells to T cells and the inclusion of MHC class II-restricted tumor antigens. identification of MHC class II-restricted tumor antigens, which are capable of stimulating CD4+ T cells, not only aids our understanding of the host immune responses against cancer antigens, but also provides opportunities for developing effective cancer vaccines.
1998 12445287 A large set of peptide antigens presented by class I major histocompatibility complex (MHC) molecules on human and murine melanomas and recognized by CD8+ T cells have been defined.
1999 12445291 In natural immune responses CD4+ T helper (Th) cells, reactive with peptide antigens presented by major histocompatibility complex (MHC) class II molecules on dendritic cells (DC), can drive the maturation of DC that is required for induction of CD8+ cytolytic T-lymphocyte (CTL) immunity.
2000 12445291 Proper induction, expansion and maintenance of CTL responses are achieved through delicate interactions between CD4+ T cells, DC and CD8+ T cells involving several ligand-receptor pairs.
2001 12445291 Th cells to a large extent operate through up-regulation of CD40L, which then interacts with CD40 on DC to cause DC maturation.
2002 12445291 Subsequent CTL induction by activated DC requires CD80/CD86 on the DC to interact with the CD28 costimulatory receptor on CD8+ T cells.
2003 12445291 Alternative molecular triggers of DC activation that can support induction of powerful CTL responses include agonistic anti-CD40 antibody or ligands of Toll-like receptors (TLR) such as LPS (TLR4 ligand) or oligodeoxynucleotides containing CpG-motifs (TLR9 ligand).
2004 12450698 In order to induce effective CTL responses against most infections and tumours, DCs must prime both CD4(+) and CD8(+) antigen-specific T cells.
2005 12450698 In this study, the infection of immature mouse bone marrow-derived DCs (BMDCs) with recombinant adenovirus (rAd) vectors led to a marked upregulation of surface costimulatory molecules, IL-12 p40 production and capacity to stimulate both allogeneic and antigen-specific T cells.
2006 12450698 Furthermore, infection of immature and mature BMDCs with a rAd encoding chicken ovalbumin (OVA) led to presentation of the antigen to TCR-transgenic OVA-specific CD4(+) and CD8(+) T cells.
2007 12450698 In addition, the activation state of responding CD8(+) T cells was further amplified if they recognised antigen on rAd-transduced BMDCs in the presence of antigen-specific CD4(+) T cells.
2008 12450698 The results suggest that rAd-encoded OVA protein is secreted by BMDCs, taken up by endocytosis and presented in association with MHC class II molecules for activation of OVA-specific CD4(+) T cells.
2009 12456590 A mouse C kappa-specific T cell clone indicates that DC-SIGN is an efficient target for antibody-mediated delivery of T cell epitopes for MHC class II presentation.
2010 12456590 The mouse C kappa -specific T cell readout was used to demonstrate that mouse mAb specific for human dendritic cell (DC)-specific ICAM-grabbing non-integrin (DC-SIGN), a novel DC-specific molecule, were 10- to 1000-fold more potent at inducing kappa-specific human CD4+ T cell proliferation compared to control mAb.
2011 12456590 These results strongly argue that DC-SIGN-specific mAb are channeled into the MHC class II presentation pathway.
2012 12456590 A mouse C kappa-specific T cell clone indicates that DC-SIGN is an efficient target for antibody-mediated delivery of T cell epitopes for MHC class II presentation.
2013 12456590 The mouse C kappa -specific T cell readout was used to demonstrate that mouse mAb specific for human dendritic cell (DC)-specific ICAM-grabbing non-integrin (DC-SIGN), a novel DC-specific molecule, were 10- to 1000-fold more potent at inducing kappa-specific human CD4+ T cell proliferation compared to control mAb.
2014 12456590 These results strongly argue that DC-SIGN-specific mAb are channeled into the MHC class II presentation pathway.
2015 12459166 Quantitative analysis of the antigen-specific IFNgamma+ T cell-mediated immune response in conventional outbred pigs: kinetics and duration of the DNA-induced IFNgamma+ CD8+ T cell response.
2016 12459166 Additional studies allowed us to show that these virus-specific IFNgamma(+) responding cells detected in this ELISPOT assay were MHC-restricted and comprised in the CD8alpha(bright) pig T cell subset.
2017 12461082 HLA-E-dependent presentation of Mtb-derived antigen to human CD8+ T cells.
2018 12461082 Recently, we have described human, Mtb-specific CD8+ cells that are neither HLA-A, B, or C nor group 1 CD1 restricted, and have found that these cells comprise the dominant CD8+ T cell response in latently infected individuals.
2019 12477426 Unfortunately, administration of soluble proteins alone generally does not induce CD8+ T cells presumably because antigen derived peptides are not introduced into the major histocompatibility complex (MHC) class I antigen presentation pathway.
2020 12481940 Vaccinating mice with DNA encoding the thyrotropin receptor (TSHR), the major autoantigen in Graves' disease, induces memory T cells that secrete interferon-gamma (IFN-gamma) in response to TSHR antigen.
2021 12481940 In initial studies, challenge of splenocytes with TSHR protein induced IFN-gamma and tumor necrosis factor-alpha (TNF-alpha) production in all three strains of mice.
2022 12481940 In summary, we report that TSHR DNA vaccination of BALB/c and NOD.H-2h4 mice, with different major histocompatibility complex (MHC) class II genes (I-Ad and I-Ak, respectively), recognize restricted, nonoverlapping TSHR T-cell epitopes, nearly all in the TSHR A subunit.
2023 12502804 Correlations between the level of IFN-gamma-secreting T cells and viral load within the MHC class I HLA supertypes should be considered in HIV vaccine design and efficacy trials.
2024 12502869 The lipopeptides were processed by dendritic cells and presented to CD8(+) T cells specific for the HLA-A*0201-restricted Pol(476-484) and the HLA-A*0301-restricted Nef(73-82) epitope, respectively.
2025 12505709 First, we compared the ELISpot-IFNgamma assay, intracellular IFNgamma staining and HLA class I tetramer-binding assay to quantify the HIV-specific CD8 T cells.
2026 12505709 Our results show that: (1) Flow cytometry and ELISpot assay measuring IFNgamma production give the same frequency of HIV-specific CD8 T cells; (2) tetramer-binding assay detects more HIV-specific CD8 T cells than other methods; (3) pools of optimal peptides and sum frequencies of individual optimal peptides give similar results in ELISpot assay; (4) ELISpot assays using peptides are more sensitive than those using rVV; and (5) CRA and ELISpot assay when using rVV provide a comparable profile of HIV antigen recognition by memory CTLs (CRA) and effector CTLs (ELISpot) in two thirds cases.
2027 12507814 We identified two abundant self peptides, IFI-6-16(74-82) and Hsp90beta(570-578), that were induced or upregulated, respectively, following infection.
2028 12507814 CD8+ T cells capable of recognizing the self-peptides in the context of HLA-A*0201 were detectable at low basal levels in the neonatal and adult human T cell repertoire, but were functionally silent.
2029 12507820 We used the resources of Mayo Clinic's tissue typing laboratory for serotyping class I HLA-A and HLA-B alleles via microlymphocytotoxicity assays.
2030 12507820 We found no statistically significant associations with class I HLA-A but did find associations with class I HLA-B, which includes alleles associated with seronegativity (B8, B13, and B44) and those associated with seropositivity (B7 and B51).
2031 12507820 We used the resources of Mayo Clinic's tissue typing laboratory for serotyping class I HLA-A and HLA-B alleles via microlymphocytotoxicity assays.
2032 12507820 We found no statistically significant associations with class I HLA-A but did find associations with class I HLA-B, which includes alleles associated with seronegativity (B8, B13, and B44) and those associated with seropositivity (B7 and B51).
2033 12512800 BMDC were generated from bone marrow precursor cells as described previously by culturing the cells in medium containing GM-CSF and IL-4.
2034 12512800 Forty to fifty percent of both samples, frozen/thawed as well as fresh BMDC, exhibited characteristic DC morphology, and the DC obtained from the frozen/thawed samples expressed a similar level of MHC class I-, MHC class II-, CD80-, CD86-, CD11c-, CD11b-, CD54- and CD205-molecule as fresh DC.
2035 12513792 The phenotype of DC was detected by FCM with CD1a, CD40, CD80, CD86, HLA-A, B, C and HLA-DR monoclonal antibodies.
2036 12513792 The level of IL-12 and IFN-gamma in supernatant of DC culture was measured by ELISA.
2037 12513792 A high expression of phenotypes was found in HL-60-DC and THP-1-DC stimulated by GM-CSF + IL-4 + TNF-gamma and K562-DC with GM-CSF + IL-4 + IL-12.
2038 12518065 Here we report the identification of an immunodominant HLA-A*0201-restricted epitope that is recognized by cytotoxic CD8(+) T cells and conserved among Orthopoxvirus species including variola virus.
2039 12543794 By comparison with local cadaver controls typed for HLA class I (n = 946) and II (n = 144) antigens, HPV-16-positive high grade vulval intraepithelial neoplasia patients (n = 42) showed significantly different frequencies of HLA-A2 [odds ratio (OR), 2.1; confidence interval (CI), 1.4-3.9], HLA-B7 (OR, 2.6; CI, 1.4-4.7), HLA-DRB1*01(01/02/04) (OR, 0.1; CI, 0.03-0.5), HLA-DRB1*11 (OR, 3.3; CI, 1.4-7.1), HLA-DRB1*13 (OR, 0), HLA-DQB1*05 (OR, 0.2; CI, 0.05-0.6), and HLA-DQB1*03032 (OR, 4.6; CI, 1.5-14.0).
2040 12545248 In this study we tested responding peripheral mononuclear cells from a patient with pancreatic adenocarcinoma who had received intradermal peptide vaccination with a mixture of 17-mer mutant ras peptides and granulocyte-macrophage colony-stimulating factor as an adjuvant.
2041 12545248 Responding peripheral T-cells were cloned by limiting dilution and several CD8(+) cytotoxic T-lymphocytes, specific for the K- RAS 12-Cys mutation were obtained.
2042 12545248 The cytotoxic T-lymphocytes were capable of killing target cells expressing HLA-A*0302 that coexpressed the K- RAS 12-Cys mutation after transfection.
2043 12547598 Immature human DC were generated from peripheral blood monocytes cultured with GM-CSF and IL-4.
2044 12547598 Uptake of antigen by DC and the degree of expression of the cell surface markers MHC class II, CD80, CD86 and the DC maturation marker CD83, was investigated by flow cytometry following incubation with liposomes or solution containing FITC-conjugated antigen.
2045 12554523 Stable transgenic expression of IL-2 and HSV1-tk by single and fusion tumor cell lines bearing EWS/FLI-1 chimeric genes.
2046 12554523 IL-2 expressing clones derived from the A673 cell line demonstrated decreased expression of HLA class I molecules compared with the parental cell line and corresponding clones derived from RD-ES.
2047 12554523 However, IFN-gamma could upregulate the expression of HLA class I antigens by IL-2 transfected A673 cells.
2048 12554523 Stable transgenic expression of IL-2 and HSV1-tk by single and fusion tumor cell lines bearing EWS/FLI-1 chimeric genes.
2049 12554523 IL-2 expressing clones derived from the A673 cell line demonstrated decreased expression of HLA class I molecules compared with the parental cell line and corresponding clones derived from RD-ES.
2050 12554523 However, IFN-gamma could upregulate the expression of HLA class I antigens by IL-2 transfected A673 cells.
2051 12560562 The specific anti-pp65 cytotoxic T lymphocyte (CTL) response restricted by HLA-G in triple transgenic mice (HLA-G, human beta2m, human CD8alpha) was then investigated by injection of dendritic cells loaded with synthetic pp65-derived peptides or by infection with canarypox virus expressing pp65.
2052 12560562 Results showed that CTLs from HLA-G mice have the capacity to kill target cells either infected with recombinant vaccinia viruses expressing pp65 or loaded with specific pp65-derived peptides using HLA-G as an antigen-presenting molecule.
2053 12560562 Moreover, using HLA-G tetramers refolded with a synthetic pp65-derived peptide, peptide-specific CD8(+) cells restricted by HLA-G have been detected in vivo.
2054 12562331 Recombinant vaccinia virus (rVV) and recombinant fowlpox virus (rFPV), expressing individual BRSV proteins, were used to demonstrate that the F, N and M2 proteins were the major antigens recognized by bovine CD8+ T cells in major histocompatibility complex (MHC)-defined cattle.
2055 12562331 BRSV protein recognition by CD8+ T cells was analysed using cytotoxic T lymphocyte (CTL) assays or by the production of interferon-gamma (IFN-gamma) following restimulation with BRSV proteins.
2056 12562331 Although there is variation in the number of expressed MHC genes in cattle with different class I haplotypes, this did not appear to influence BRSV protein recognition by CD8+ T cells.
2057 12562331 Recombinant vaccinia virus (rVV) and recombinant fowlpox virus (rFPV), expressing individual BRSV proteins, were used to demonstrate that the F, N and M2 proteins were the major antigens recognized by bovine CD8+ T cells in major histocompatibility complex (MHC)-defined cattle.
2058 12562331 BRSV protein recognition by CD8+ T cells was analysed using cytotoxic T lymphocyte (CTL) assays or by the production of interferon-gamma (IFN-gamma) following restimulation with BRSV proteins.
2059 12562331 Although there is variation in the number of expressed MHC genes in cattle with different class I haplotypes, this did not appear to influence BRSV protein recognition by CD8+ T cells.
2060 12573052 Antigen presenting cells (APC) encounter most protein and vaccine immunogens as extracellular proteins and, thus, present them on major histocompatibility complex (MHC) class II molecules leading to the activation of CD4(+) T cells.
2061 12573052 Protein antigens encoded by nucleic acids delivered to dendritic cell (DC) are produced inside the cell and, thus, can stimulate MHC class I mediated activation of CD8(+) T-cell immune responses.
2062 12573052 Antigen presenting cells (APC) encounter most protein and vaccine immunogens as extracellular proteins and, thus, present them on major histocompatibility complex (MHC) class II molecules leading to the activation of CD4(+) T cells.
2063 12573052 Protein antigens encoded by nucleic acids delivered to dendritic cell (DC) are produced inside the cell and, thus, can stimulate MHC class I mediated activation of CD8(+) T-cell immune responses.
2064 12579325 Chemoimmunotherapy in mice carrying HPV16-associated, MHC class I+ and class I- tumours: Effects of CBM-4A potentiated with IL-2, IL-12, GM-CSF and genetically modified tumour vaccines.
2065 12579325 The effectiveness of chemoimmunotherapy with ifosfamide derivative CBM-4A and recombinant IL-2, IL-12, GM-CSF, or genetically modified, cytokine-producing tumour vaccines was examined in mice carrying HPV16-associated, MHC class I+ (TC-1), and MHC class I- (MK16) tumours.
2066 12579325 When the i.p. treatment of the MHC class I+ TC-1 tumour-bearing mice with CBM-4A was followed by peritumoral s.c. administration of IL-2, IL-12, or both cytokines, the growth of TC1 tumours was inhibited more vigorously than after the chemotherapy alone.
2067 12579325 In contrast, when the i.p. treatment ofEthe MHC class I- MK16 tumour-bearing mice with CBM-4A was followed by peritumoral s.c. administration of IL-2 or IL-12, the cytokine therapy had no potentiating effect.
2068 12579325 CBM-4A pretreatment was followed by peritumoral s.c. administration of IL-2 plus IL-12.
2069 12579325 InEfurther experiments, the TC-1 and MK16 tumour-bearing mice were i.p. pretreated with CBM-4A and then injected s.c., peritumorally, with genetically modified, IL-2 or GM-CSF-producing MK16 tumour vaccines.
2070 12579325 MK16 neoplasms, which were pretreated i.p. with CBM-4A, and then injected peritumorally with IL-2 or GM-CSF.
2071 12579325 Peritumoral administration of GM-CSF had no antimetastatic effect, whereas peritumoral IL-2 administration produced substantial reduction of lung metastases.
2072 12579325 Taken collectively, the results indicate that in mice carrying the MK16 (MHC class I-) tumour, the effects of the adjuvant cytokine therapy were substantially weaker than in mice carrying the TC-1 (MHC class I+) tumour inoculum.
2073 12579325 Chemoimmunotherapy in mice carrying HPV16-associated, MHC class I+ and class I- tumours: Effects of CBM-4A potentiated with IL-2, IL-12, GM-CSF and genetically modified tumour vaccines.
2074 12579325 The effectiveness of chemoimmunotherapy with ifosfamide derivative CBM-4A and recombinant IL-2, IL-12, GM-CSF, or genetically modified, cytokine-producing tumour vaccines was examined in mice carrying HPV16-associated, MHC class I+ (TC-1), and MHC class I- (MK16) tumours.
2075 12579325 When the i.p. treatment of the MHC class I+ TC-1 tumour-bearing mice with CBM-4A was followed by peritumoral s.c. administration of IL-2, IL-12, or both cytokines, the growth of TC1 tumours was inhibited more vigorously than after the chemotherapy alone.
2076 12579325 In contrast, when the i.p. treatment ofEthe MHC class I- MK16 tumour-bearing mice with CBM-4A was followed by peritumoral s.c. administration of IL-2 or IL-12, the cytokine therapy had no potentiating effect.
2077 12579325 CBM-4A pretreatment was followed by peritumoral s.c. administration of IL-2 plus IL-12.
2078 12579325 InEfurther experiments, the TC-1 and MK16 tumour-bearing mice were i.p. pretreated with CBM-4A and then injected s.c., peritumorally, with genetically modified, IL-2 or GM-CSF-producing MK16 tumour vaccines.
2079 12579325 MK16 neoplasms, which were pretreated i.p. with CBM-4A, and then injected peritumorally with IL-2 or GM-CSF.
2080 12579325 Peritumoral administration of GM-CSF had no antimetastatic effect, whereas peritumoral IL-2 administration produced substantial reduction of lung metastases.
2081 12579325 Taken collectively, the results indicate that in mice carrying the MK16 (MHC class I-) tumour, the effects of the adjuvant cytokine therapy were substantially weaker than in mice carrying the TC-1 (MHC class I+) tumour inoculum.
2082 12579325 Chemoimmunotherapy in mice carrying HPV16-associated, MHC class I+ and class I- tumours: Effects of CBM-4A potentiated with IL-2, IL-12, GM-CSF and genetically modified tumour vaccines.
2083 12579325 The effectiveness of chemoimmunotherapy with ifosfamide derivative CBM-4A and recombinant IL-2, IL-12, GM-CSF, or genetically modified, cytokine-producing tumour vaccines was examined in mice carrying HPV16-associated, MHC class I+ (TC-1), and MHC class I- (MK16) tumours.
2084 12579325 When the i.p. treatment of the MHC class I+ TC-1 tumour-bearing mice with CBM-4A was followed by peritumoral s.c. administration of IL-2, IL-12, or both cytokines, the growth of TC1 tumours was inhibited more vigorously than after the chemotherapy alone.
2085 12579325 In contrast, when the i.p. treatment ofEthe MHC class I- MK16 tumour-bearing mice with CBM-4A was followed by peritumoral s.c. administration of IL-2 or IL-12, the cytokine therapy had no potentiating effect.
2086 12579325 CBM-4A pretreatment was followed by peritumoral s.c. administration of IL-2 plus IL-12.
2087 12579325 InEfurther experiments, the TC-1 and MK16 tumour-bearing mice were i.p. pretreated with CBM-4A and then injected s.c., peritumorally, with genetically modified, IL-2 or GM-CSF-producing MK16 tumour vaccines.
2088 12579325 MK16 neoplasms, which were pretreated i.p. with CBM-4A, and then injected peritumorally with IL-2 or GM-CSF.
2089 12579325 Peritumoral administration of GM-CSF had no antimetastatic effect, whereas peritumoral IL-2 administration produced substantial reduction of lung metastases.
2090 12579325 Taken collectively, the results indicate that in mice carrying the MK16 (MHC class I-) tumour, the effects of the adjuvant cytokine therapy were substantially weaker than in mice carrying the TC-1 (MHC class I+) tumour inoculum.
2091 12579325 Chemoimmunotherapy in mice carrying HPV16-associated, MHC class I+ and class I- tumours: Effects of CBM-4A potentiated with IL-2, IL-12, GM-CSF and genetically modified tumour vaccines.
2092 12579325 The effectiveness of chemoimmunotherapy with ifosfamide derivative CBM-4A and recombinant IL-2, IL-12, GM-CSF, or genetically modified, cytokine-producing tumour vaccines was examined in mice carrying HPV16-associated, MHC class I+ (TC-1), and MHC class I- (MK16) tumours.
2093 12579325 When the i.p. treatment of the MHC class I+ TC-1 tumour-bearing mice with CBM-4A was followed by peritumoral s.c. administration of IL-2, IL-12, or both cytokines, the growth of TC1 tumours was inhibited more vigorously than after the chemotherapy alone.
2094 12579325 In contrast, when the i.p. treatment ofEthe MHC class I- MK16 tumour-bearing mice with CBM-4A was followed by peritumoral s.c. administration of IL-2 or IL-12, the cytokine therapy had no potentiating effect.
2095 12579325 CBM-4A pretreatment was followed by peritumoral s.c. administration of IL-2 plus IL-12.
2096 12579325 InEfurther experiments, the TC-1 and MK16 tumour-bearing mice were i.p. pretreated with CBM-4A and then injected s.c., peritumorally, with genetically modified, IL-2 or GM-CSF-producing MK16 tumour vaccines.
2097 12579325 MK16 neoplasms, which were pretreated i.p. with CBM-4A, and then injected peritumorally with IL-2 or GM-CSF.
2098 12579325 Peritumoral administration of GM-CSF had no antimetastatic effect, whereas peritumoral IL-2 administration produced substantial reduction of lung metastases.
2099 12579325 Taken collectively, the results indicate that in mice carrying the MK16 (MHC class I-) tumour, the effects of the adjuvant cytokine therapy were substantially weaker than in mice carrying the TC-1 (MHC class I+) tumour inoculum.
2100 12584740 Previous studies have shown that 5-fluorouracil (5-FU) can upregulate the expression of membrane-associated carcino-embryonic antigen (CEA), and MHC molecules in colon and breast carcinoma cell lines.
2101 12584740 The CEA peptide-specific CTLs generated in our laboratory from normal HLA-A(*)02.01(+) donor PBMCs, were able to kill HLA-A(*)02.01(+)/CEA(+) breast (MCF-7-T103) and colon (HLA-A(*)02.01 gene-transfected HT-29 and C22.20) carcinoma cells in HLA-A(*)02.01 restricted manner.
2102 12584740 Previous studies have shown that 5-fluorouracil (5-FU) can upregulate the expression of membrane-associated carcino-embryonic antigen (CEA), and MHC molecules in colon and breast carcinoma cell lines.
2103 12584740 The CEA peptide-specific CTLs generated in our laboratory from normal HLA-A(*)02.01(+) donor PBMCs, were able to kill HLA-A(*)02.01(+)/CEA(+) breast (MCF-7-T103) and colon (HLA-A(*)02.01 gene-transfected HT-29 and C22.20) carcinoma cells in HLA-A(*)02.01 restricted manner.
2104 12588661 Major histocompatibility complex (MHC) H-2b-expressing mice (C57BL/6) secreted interferon-gamma (IFN-gamma) after stimulation with peptides from the regions 1-20, 41-50, 81-110, 121-150 and 161-193 of the MPB70 sequence.
2105 12590704 4-1BB ligand stimulation enhances myeloid dendritic cell maturation from human umbilical cord blood CD34+ progenitor cells.
2106 12590704 We investigated whether 4-1BB ligand (4-1BBL), a member of the tumor necrosis factor (TNF) family, is involved in the maturation process to mature myeloid DCs during in vitro DC differentiation from immature DCs derived from human umbilical cord blood (CB) CD34(+) progenitor cells.
2107 12590704 Enhanced levels of CD11c as well as immunostimulatory molecules such as CD86, MHC class II, and 4-1BBL were induced in response to 4-1BBL stimulation.
2108 12590704 Stimulation of 4-1BBL on DCs with 4-1BB-Fc or with 4-1BB-transfected Jurkat cells resulted in acquisition of capacity for the immature DCs to produce interleukin-12 (IL-12).
2109 12634406 Use of transgenic HLA A*0201/Kb and HHD II mice to evaluate frequency of cytomegalovirus IE1-derived peptide usage in eliciting human CD8 cytokine response.
2110 12634406 Unlike the pp65 protein of human cytomegalovirus (CMV), which has an immunodominant peptide, pp65(495-503), recognized by human CD8(+) cells in the context of HLA A*0201, the fine peptide specificity for CMV IE1 has shown no such immunodominance.
2111 12634406 Based on an intracellular gamma interferon response, IE1(p297-304), a previously unrecognized CD8 epitope, triggered a prominent response to CMV IE1 in HLA A*0201 subjects.
2112 12634406 Use of transgenic HLA A*0201/Kb and HHD II mice to evaluate frequency of cytomegalovirus IE1-derived peptide usage in eliciting human CD8 cytokine response.
2113 12634406 Unlike the pp65 protein of human cytomegalovirus (CMV), which has an immunodominant peptide, pp65(495-503), recognized by human CD8(+) cells in the context of HLA A*0201, the fine peptide specificity for CMV IE1 has shown no such immunodominance.
2114 12634406 Based on an intracellular gamma interferon response, IE1(p297-304), a previously unrecognized CD8 epitope, triggered a prominent response to CMV IE1 in HLA A*0201 subjects.
2115 12634406 Use of transgenic HLA A*0201/Kb and HHD II mice to evaluate frequency of cytomegalovirus IE1-derived peptide usage in eliciting human CD8 cytokine response.
2116 12634406 Unlike the pp65 protein of human cytomegalovirus (CMV), which has an immunodominant peptide, pp65(495-503), recognized by human CD8(+) cells in the context of HLA A*0201, the fine peptide specificity for CMV IE1 has shown no such immunodominance.
2117 12634406 Based on an intracellular gamma interferon response, IE1(p297-304), a previously unrecognized CD8 epitope, triggered a prominent response to CMV IE1 in HLA A*0201 subjects.
2118 12637770 Class II MHC molecules present processed peptides from exogenous antigens to CD4+ helper T lymphocytes.
2119 12637770 Current research is focused on understanding the situations where class II MHC gene expression occurs in a CIITA-independent pathway, and the molecular basis for this expression.
2120 12637770 Class II MHC molecules present processed peptides from exogenous antigens to CD4+ helper T lymphocytes.
2121 12637770 Current research is focused on understanding the situations where class II MHC gene expression occurs in a CIITA-independent pathway, and the molecular basis for this expression.
2122 12645903 Application to the MHC class I molecule HLA-A*0201.
2123 12651070 Relative dominance of HLA-B*07 restricted CD8+ T-lymphocyte immune responses to human cytomegalovirus pp65 in persons sharing HLA-A*02 and HLA-B*07 alleles.
2124 12651070 CD8(+) T-cell responses to three human cytomegalovirus (CMV) pp65 epitopes were studied in panels of healthy seropositive HLA-A*02/HLA-B*07 individuals, and HLA-A*02 donors mismatched for HLA-B*07.
2125 12651070 Similar immunodominance of HLA-B*07 over HLA-A*02 was found in two immunocompromised HIV-infected HLA-A*02/HLA-B*07 patients, and in the reconstituting immune system of three stem cell transplant recipients.
2126 12651070 In vitro stimulation of peripheral blood mononuclear cells (PBMC) from two immunocompetent HLA-A*02/HLA-B*07 individuals indicated that cytotoxic T lymphocyte (CTL) precursors specific for both HLA-A*02 and HLA-B*07 restricted epitopes were present and could be expanded by stimulation with the cognate peptides.
2127 12651070 Our results indicate that CMV-specific cellular immune responses restricted by HLA-B*07 dominate those restricted by HLA-A*02 in both immunocompetent and immunocompromised individuals.
2128 12651070 Relative dominance of HLA-B*07 restricted CD8+ T-lymphocyte immune responses to human cytomegalovirus pp65 in persons sharing HLA-A*02 and HLA-B*07 alleles.
2129 12651070 CD8(+) T-cell responses to three human cytomegalovirus (CMV) pp65 epitopes were studied in panels of healthy seropositive HLA-A*02/HLA-B*07 individuals, and HLA-A*02 donors mismatched for HLA-B*07.
2130 12651070 Similar immunodominance of HLA-B*07 over HLA-A*02 was found in two immunocompromised HIV-infected HLA-A*02/HLA-B*07 patients, and in the reconstituting immune system of three stem cell transplant recipients.
2131 12651070 In vitro stimulation of peripheral blood mononuclear cells (PBMC) from two immunocompetent HLA-A*02/HLA-B*07 individuals indicated that cytotoxic T lymphocyte (CTL) precursors specific for both HLA-A*02 and HLA-B*07 restricted epitopes were present and could be expanded by stimulation with the cognate peptides.
2132 12651070 Our results indicate that CMV-specific cellular immune responses restricted by HLA-B*07 dominate those restricted by HLA-A*02 in both immunocompetent and immunocompromised individuals.
2133 12651070 Relative dominance of HLA-B*07 restricted CD8+ T-lymphocyte immune responses to human cytomegalovirus pp65 in persons sharing HLA-A*02 and HLA-B*07 alleles.
2134 12651070 CD8(+) T-cell responses to three human cytomegalovirus (CMV) pp65 epitopes were studied in panels of healthy seropositive HLA-A*02/HLA-B*07 individuals, and HLA-A*02 donors mismatched for HLA-B*07.
2135 12651070 Similar immunodominance of HLA-B*07 over HLA-A*02 was found in two immunocompromised HIV-infected HLA-A*02/HLA-B*07 patients, and in the reconstituting immune system of three stem cell transplant recipients.
2136 12651070 In vitro stimulation of peripheral blood mononuclear cells (PBMC) from two immunocompetent HLA-A*02/HLA-B*07 individuals indicated that cytotoxic T lymphocyte (CTL) precursors specific for both HLA-A*02 and HLA-B*07 restricted epitopes were present and could be expanded by stimulation with the cognate peptides.
2137 12651070 Our results indicate that CMV-specific cellular immune responses restricted by HLA-B*07 dominate those restricted by HLA-A*02 in both immunocompetent and immunocompromised individuals.
2138 12651070 Relative dominance of HLA-B*07 restricted CD8+ T-lymphocyte immune responses to human cytomegalovirus pp65 in persons sharing HLA-A*02 and HLA-B*07 alleles.
2139 12651070 CD8(+) T-cell responses to three human cytomegalovirus (CMV) pp65 epitopes were studied in panels of healthy seropositive HLA-A*02/HLA-B*07 individuals, and HLA-A*02 donors mismatched for HLA-B*07.
2140 12651070 Similar immunodominance of HLA-B*07 over HLA-A*02 was found in two immunocompromised HIV-infected HLA-A*02/HLA-B*07 patients, and in the reconstituting immune system of three stem cell transplant recipients.
2141 12651070 In vitro stimulation of peripheral blood mononuclear cells (PBMC) from two immunocompetent HLA-A*02/HLA-B*07 individuals indicated that cytotoxic T lymphocyte (CTL) precursors specific for both HLA-A*02 and HLA-B*07 restricted epitopes were present and could be expanded by stimulation with the cognate peptides.
2142 12651070 Our results indicate that CMV-specific cellular immune responses restricted by HLA-B*07 dominate those restricted by HLA-A*02 in both immunocompetent and immunocompromised individuals.
2143 12651070 Relative dominance of HLA-B*07 restricted CD8+ T-lymphocyte immune responses to human cytomegalovirus pp65 in persons sharing HLA-A*02 and HLA-B*07 alleles.
2144 12651070 CD8(+) T-cell responses to three human cytomegalovirus (CMV) pp65 epitopes were studied in panels of healthy seropositive HLA-A*02/HLA-B*07 individuals, and HLA-A*02 donors mismatched for HLA-B*07.
2145 12651070 Similar immunodominance of HLA-B*07 over HLA-A*02 was found in two immunocompromised HIV-infected HLA-A*02/HLA-B*07 patients, and in the reconstituting immune system of three stem cell transplant recipients.
2146 12651070 In vitro stimulation of peripheral blood mononuclear cells (PBMC) from two immunocompetent HLA-A*02/HLA-B*07 individuals indicated that cytotoxic T lymphocyte (CTL) precursors specific for both HLA-A*02 and HLA-B*07 restricted epitopes were present and could be expanded by stimulation with the cognate peptides.
2147 12651070 Our results indicate that CMV-specific cellular immune responses restricted by HLA-B*07 dominate those restricted by HLA-A*02 in both immunocompetent and immunocompromised individuals.
2148 12664058 Recently the Coxsackie and adenovirus receptor (CAR) has been shown to mediate adenoviral entry into tumour cells, although previous studies also suggested a role for MHC class I heavy chain.
2149 12664058 Detailed evaluation of the expression of both CAR and MHC class I in prostate cancer cell lines would have important implications for therapeutic strategies.
2150 12664058 We have found that, unlike cell lines derived from other malignancies, in human and murine prostate cancer loss of CAR expression appears to be relatively infrequent and does not correlate with loss of MHC class I expression.
2151 12664058 Recently the Coxsackie and adenovirus receptor (CAR) has been shown to mediate adenoviral entry into tumour cells, although previous studies also suggested a role for MHC class I heavy chain.
2152 12664058 Detailed evaluation of the expression of both CAR and MHC class I in prostate cancer cell lines would have important implications for therapeutic strategies.
2153 12664058 We have found that, unlike cell lines derived from other malignancies, in human and murine prostate cancer loss of CAR expression appears to be relatively infrequent and does not correlate with loss of MHC class I expression.
2154 12664058 Recently the Coxsackie and adenovirus receptor (CAR) has been shown to mediate adenoviral entry into tumour cells, although previous studies also suggested a role for MHC class I heavy chain.
2155 12664058 Detailed evaluation of the expression of both CAR and MHC class I in prostate cancer cell lines would have important implications for therapeutic strategies.
2156 12664058 We have found that, unlike cell lines derived from other malignancies, in human and murine prostate cancer loss of CAR expression appears to be relatively infrequent and does not correlate with loss of MHC class I expression.
2157 12668642 Quantitation of CD8+ T cell responses to newly identified HLA-A*0201-restricted T cell epitopes conserved among vaccinia and variola (smallpox) viruses.
2158 12668642 In this report, we identified two CD8+ T cell epitopes restricted by the most common human major histocompatibility complex (MHC) class I allele, HLA-A*0201.
2159 12668642 The frequency of vaccinia-specific CD8+ T cell responses to these epitopes measured by interferon (IFN)-gamma enzyme-linked immunospot (ELISPOT) assay and HLA/peptide tetramer staining peaked 2 wk after primary immunization and then declined, but were still detectable 1 to 3 yr after primary immunization. 2 wk after immunization, IFN-gamma-producing cells specific to these two epitopes were 14% of total vaccinia virus-specific IFN-gamma-producing cells in one donor, 35% in the second donor, and 6% in the third donor.
2160 12668642 Quantitation of CD8+ T cell responses to newly identified HLA-A*0201-restricted T cell epitopes conserved among vaccinia and variola (smallpox) viruses.
2161 12668642 In this report, we identified two CD8+ T cell epitopes restricted by the most common human major histocompatibility complex (MHC) class I allele, HLA-A*0201.
2162 12668642 The frequency of vaccinia-specific CD8+ T cell responses to these epitopes measured by interferon (IFN)-gamma enzyme-linked immunospot (ELISPOT) assay and HLA/peptide tetramer staining peaked 2 wk after primary immunization and then declined, but were still detectable 1 to 3 yr after primary immunization. 2 wk after immunization, IFN-gamma-producing cells specific to these two epitopes were 14% of total vaccinia virus-specific IFN-gamma-producing cells in one donor, 35% in the second donor, and 6% in the third donor.
2163 12670905 Suboptimal activation of CD8(+) T cells by melanoma-derived altered peptide ligands: role of Melan-A/MART-1 optimized analogues.
2164 12670905 We recently demonstrated that Melan-A/MART-1-reactive CTLs can be anergized by peptide analogues with partial agonist/antagonist functions, which selectively impair interleukin (IL)-2 release.
2165 12670905 HLA-bound peptide fractions were eluted from HLA-A*0201/Melan-A/MART-1(+) melanoma cells and analyzed for reconstitution of the MART-1-specific T-cell epitope.
2166 12670905 Among the peptide fractions able to induce IFN-gamma release by MART-1-specific T cells, only fraction 43-44 activated IL-2 production by anti-MART-1 T cells, whereas the remaining two fractions acted as peptide antagonists by inhibiting IL-2 release in response to the native epitope.
2167 12670905 A comparable down-modulation of IL-2 release could also be induced by the MART-1-derived peptide 32-40, previously identified in one of the two anergizing fractions.
2168 12670905 A substantial deficit in IL-2 release was additionally detected in tumor-specific CD8(+) T cells infiltrating melanoma lesions.
2169 12670905 To overcome IL-2 impairment by peptide antagonists, anti-MART-1 T cells were generated by in vitro sensitization with the two optimized analogues Melan-A/MART-1(27-35) 1L (with superagonist features) and Melan-A/MART-1(26-35) 2L (with improved HLA-A*0201 binding).
2170 12670905 T cells raised with the superagonist Melan-A/MART-1(27-35) 1L showed resistance to the inhibition of IL-2 release mediated by melanoma-derived peptide fractions, whereas Melan-A/MART-1(26-35) 2L-specific T cells appeared to be as sensitive as T cells raised with the parental epitope.
2171 12670905 This resistance was associated with the enhanced ability of Melan-A/MART-1(27-35) 1L-specific T cells to release IL-2.
2172 12670905 Suboptimal activation of CD8(+) T cells by melanoma-derived altered peptide ligands: role of Melan-A/MART-1 optimized analogues.
2173 12670905 We recently demonstrated that Melan-A/MART-1-reactive CTLs can be anergized by peptide analogues with partial agonist/antagonist functions, which selectively impair interleukin (IL)-2 release.
2174 12670905 HLA-bound peptide fractions were eluted from HLA-A*0201/Melan-A/MART-1(+) melanoma cells and analyzed for reconstitution of the MART-1-specific T-cell epitope.
2175 12670905 Among the peptide fractions able to induce IFN-gamma release by MART-1-specific T cells, only fraction 43-44 activated IL-2 production by anti-MART-1 T cells, whereas the remaining two fractions acted as peptide antagonists by inhibiting IL-2 release in response to the native epitope.
2176 12670905 A comparable down-modulation of IL-2 release could also be induced by the MART-1-derived peptide 32-40, previously identified in one of the two anergizing fractions.
2177 12670905 A substantial deficit in IL-2 release was additionally detected in tumor-specific CD8(+) T cells infiltrating melanoma lesions.
2178 12670905 To overcome IL-2 impairment by peptide antagonists, anti-MART-1 T cells were generated by in vitro sensitization with the two optimized analogues Melan-A/MART-1(27-35) 1L (with superagonist features) and Melan-A/MART-1(26-35) 2L (with improved HLA-A*0201 binding).
2179 12670905 T cells raised with the superagonist Melan-A/MART-1(27-35) 1L showed resistance to the inhibition of IL-2 release mediated by melanoma-derived peptide fractions, whereas Melan-A/MART-1(26-35) 2L-specific T cells appeared to be as sensitive as T cells raised with the parental epitope.
2180 12670905 This resistance was associated with the enhanced ability of Melan-A/MART-1(27-35) 1L-specific T cells to release IL-2.
2181 12672905 We showed that BCG could promote cord blood monocyte-derived DC maturation by up-regulation of CD80, CD83, CD86, CD40, and MHC class II molecules and down-regulation of mannose receptor.
2182 12672905 BCG was able to induce similar levels of tumor necrosis factor-alpha and IL-10 but no bioactive IL-12p70 production from cord blood DCs as from adult blood DCs.
2183 12672905 Both non-BCG-treated and BCG-treated cord blood DCs efficiently induced a high level of IL-10, medium level of interferon-gamma, but little IL-4 production by cord blood naïve CD4+ T cells.
2184 12672905 Heat shock protein 65, a key component of BCG, had no effect on cord blood DC maturation in terms of CD86, MHC class II, and mannose receptor up-regulation.
2185 12672905 We showed that BCG could promote cord blood monocyte-derived DC maturation by up-regulation of CD80, CD83, CD86, CD40, and MHC class II molecules and down-regulation of mannose receptor.
2186 12672905 BCG was able to induce similar levels of tumor necrosis factor-alpha and IL-10 but no bioactive IL-12p70 production from cord blood DCs as from adult blood DCs.
2187 12672905 Both non-BCG-treated and BCG-treated cord blood DCs efficiently induced a high level of IL-10, medium level of interferon-gamma, but little IL-4 production by cord blood naïve CD4+ T cells.
2188 12672905 Heat shock protein 65, a key component of BCG, had no effect on cord blood DC maturation in terms of CD86, MHC class II, and mannose receptor up-regulation.
2189 12672936 There were no differences in the percentages of CD4(+) and CD8(+) T cells between the groups, but the proportion of mature B cells [CD21(+)/major histocompatibility complex (MHC) class II(+)] was greater in those fed the probiotic.
2190 12682262 Identification and characterization of the immunodominant rat HER-2/neu MHC class I epitope presented by spontaneous mammary tumors from HER-2/neu-transgenic mice.
2191 12682262 Discovery of this epitope allows for better characterization of the CD8(+) T cell responses in the neu-N mouse model in which neu-specific tolerance must be overcome to produce effective antitumor immunity.
2192 12706680 This effect was due to activation of MHC class I-restricted CD8(+) T cells coupled with an increased secretion of proinflammatory cytokines IFN-gamma, TNF-alpha and IL-2.
2193 12706680 Also, specific activation of dendritic cells was indicated by a two-three-fold upregulation of their costimulatory CD80 and MHC class II molecules.
2194 12706680 This effect was due to activation of MHC class I-restricted CD8(+) T cells coupled with an increased secretion of proinflammatory cytokines IFN-gamma, TNF-alpha and IL-2.
2195 12706680 Also, specific activation of dendritic cells was indicated by a two-three-fold upregulation of their costimulatory CD80 and MHC class II molecules.
2196 12706709 Dengue 2 PreM-E/LAMP chimera targeted to the MHC class II compartment elicits long-lasting neutralizing antibodies.
2197 12706709 A dengue 2 plasmid DNA vaccine (pD2) expressing the pre-membrane and envelope proteins (preM-E) was modified by replacing the dengue transmembrane and cytoplasmic sequences with those of the mouse lysosome-associated membrane protein (pD2/LAMP).
2198 12706709 Immunofluorescence and confocal microscopy of human 293, NIH 3T3, and macrophage IC21 cell lines transfected with pD2/LAMP showed that the preM-E/LAMP protein chimera was present in vesicles containing endogenous LAMP and major histocompatability complex class II (MHC II), in contrast to the non-vesicular localization of native preM-E protein lacking the LAMP targeting sequence.
2199 12706709 In contrast, vaccination with pD2/LAMP resulted in PRNT(50) of 270, 320 and 160 at approximately 1, 3 and 8 months after two immunizations with 50 microg DNA, and approached 100% neutralization at 1:20 dilution.
2200 12706709 Additional immunization with pD2/LAMP, after 8 months, increased the neutralizing antibody titers to >640.
2201 12706709 The neutralizing responses to the pD2/LAMP chimera were greatly superior to those elicited by pD2 in all conditions.
2202 12706709 These results underscore the importance of MHC class II presentation of DNA-encoded dengue-virus envelope protein for production of neutralizing antibodies.
2203 12706709 Dengue 2 PreM-E/LAMP chimera targeted to the MHC class II compartment elicits long-lasting neutralizing antibodies.
2204 12706709 A dengue 2 plasmid DNA vaccine (pD2) expressing the pre-membrane and envelope proteins (preM-E) was modified by replacing the dengue transmembrane and cytoplasmic sequences with those of the mouse lysosome-associated membrane protein (pD2/LAMP).
2205 12706709 Immunofluorescence and confocal microscopy of human 293, NIH 3T3, and macrophage IC21 cell lines transfected with pD2/LAMP showed that the preM-E/LAMP protein chimera was present in vesicles containing endogenous LAMP and major histocompatability complex class II (MHC II), in contrast to the non-vesicular localization of native preM-E protein lacking the LAMP targeting sequence.
2206 12706709 In contrast, vaccination with pD2/LAMP resulted in PRNT(50) of 270, 320 and 160 at approximately 1, 3 and 8 months after two immunizations with 50 microg DNA, and approached 100% neutralization at 1:20 dilution.
2207 12706709 Additional immunization with pD2/LAMP, after 8 months, increased the neutralizing antibody titers to >640.
2208 12706709 The neutralizing responses to the pD2/LAMP chimera were greatly superior to those elicited by pD2 in all conditions.
2209 12706709 These results underscore the importance of MHC class II presentation of DNA-encoded dengue-virus envelope protein for production of neutralizing antibodies.
2210 12706709 Dengue 2 PreM-E/LAMP chimera targeted to the MHC class II compartment elicits long-lasting neutralizing antibodies.
2211 12706709 A dengue 2 plasmid DNA vaccine (pD2) expressing the pre-membrane and envelope proteins (preM-E) was modified by replacing the dengue transmembrane and cytoplasmic sequences with those of the mouse lysosome-associated membrane protein (pD2/LAMP).
2212 12706709 Immunofluorescence and confocal microscopy of human 293, NIH 3T3, and macrophage IC21 cell lines transfected with pD2/LAMP showed that the preM-E/LAMP protein chimera was present in vesicles containing endogenous LAMP and major histocompatability complex class II (MHC II), in contrast to the non-vesicular localization of native preM-E protein lacking the LAMP targeting sequence.
2213 12706709 In contrast, vaccination with pD2/LAMP resulted in PRNT(50) of 270, 320 and 160 at approximately 1, 3 and 8 months after two immunizations with 50 microg DNA, and approached 100% neutralization at 1:20 dilution.
2214 12706709 Additional immunization with pD2/LAMP, after 8 months, increased the neutralizing antibody titers to >640.
2215 12706709 The neutralizing responses to the pD2/LAMP chimera were greatly superior to those elicited by pD2 in all conditions.
2216 12706709 These results underscore the importance of MHC class II presentation of DNA-encoded dengue-virus envelope protein for production of neutralizing antibodies.
2217 12709012 However, treatment of chondrocytes with IFN-gamma up-regulated MHC class I expression and rendered the cells susceptible to lysis by CTL.
2218 12725788 Identification of MHC class II-restricted tumor antigens recognized by CD4+ T cells.
2219 12725788 Here we describe a genetic targeting expression system for cloning genes encoding for MHC class II-restricted tumor antigens recognized by tumor-reactive CD4+ T cells.
2220 12725788 Identification of MHC class II-restricted tumor antigens recognized by CD4+ T cells.
2221 12725788 Here we describe a genetic targeting expression system for cloning genes encoding for MHC class II-restricted tumor antigens recognized by tumor-reactive CD4+ T cells.
2222 12734382 DC-888mel hybrids efficiently presented HLA-A*0201-restricted epitopes from the melanoma Ags MART-1, gp100, tyrosinase, and tyrosinase-related protein 2 as evaluated by specific cytokine secretion from six distinct CTL lines.
2223 12734382 In contrast, DCs could not cross-present MHC class I-restricted epitopes after exogenously loading with gp100 protein.
2224 12734382 DC-888mel hybrids also presented HLA-DR beta 1*0401- and HLA-DR beta 1*0701-restricted peptides from gp100 to CD4(+) T cell populations.
2225 12734382 Therefore, fusions of DCs and tumor cells express both MHC class I- and class II-restricted tumor-associated epitopes and may be useful for the induction of tumor-reactive CD8(+) and CD4(+) T cells in vitro and in human vaccination trials.
2226 12734382 DC-888mel hybrids efficiently presented HLA-A*0201-restricted epitopes from the melanoma Ags MART-1, gp100, tyrosinase, and tyrosinase-related protein 2 as evaluated by specific cytokine secretion from six distinct CTL lines.
2227 12734382 In contrast, DCs could not cross-present MHC class I-restricted epitopes after exogenously loading with gp100 protein.
2228 12734382 DC-888mel hybrids also presented HLA-DR beta 1*0401- and HLA-DR beta 1*0701-restricted peptides from gp100 to CD4(+) T cell populations.
2229 12734382 Therefore, fusions of DCs and tumor cells express both MHC class I- and class II-restricted tumor-associated epitopes and may be useful for the induction of tumor-reactive CD8(+) and CD4(+) T cells in vitro and in human vaccination trials.
2230 12734382 DC-888mel hybrids efficiently presented HLA-A*0201-restricted epitopes from the melanoma Ags MART-1, gp100, tyrosinase, and tyrosinase-related protein 2 as evaluated by specific cytokine secretion from six distinct CTL lines.
2231 12734382 In contrast, DCs could not cross-present MHC class I-restricted epitopes after exogenously loading with gp100 protein.
2232 12734382 DC-888mel hybrids also presented HLA-DR beta 1*0401- and HLA-DR beta 1*0701-restricted peptides from gp100 to CD4(+) T cell populations.
2233 12734382 Therefore, fusions of DCs and tumor cells express both MHC class I- and class II-restricted tumor-associated epitopes and may be useful for the induction of tumor-reactive CD8(+) and CD4(+) T cells in vitro and in human vaccination trials.
2234 12739069 High levels of Fas ligand and MHC class II in the absence of CD80 or CD86 expression and a decreased CD4+ T cell Infiltration, enables murine skin tumours to progress.
2235 12739069 It has been hypothesized that tumour cells might evade immunological destruction by expressing Fas ligand (FasL), a molecule which induces apoptosis in Fas(+) target cells.
2236 12739069 Detailed flow cytometric analysis was used to study tumour cell expression of FasL, Fas, CD80, CD86 and MHC class II.
2237 12739069 We also analysed the percentage of apoptotic tumour cells in vivo using annexin V and correlated skin tumour progression with CD4 and CD8 T cell infiltration.
2238 12739069 The percentage of progressor tumours expressing MHC II was significantly greater than regressor tumours, while neither tumour expressed CD80 or CD86 costimulatory molecules.
2239 12739069 The results suggest that progression of skin tumours occurs if tumour cells express high levels of MHC II but not costimulatory molecules such as CD80 or CD86.
2240 12744869 Antigen entrapped in the escheriosomes leads to the generation of CD4(+) helper and CD8(+) cytotoxic T cell response.
2241 12744869 Our present study demonstrates that antigen encapsulated in escheriosomes could be successfully delivered simultaneously to the cytosolic as well as endosomal processing pathways of antigen presenting cells, leading to the generation of both CD4(+) T-helper and CD8(+) cytotoxic T cell response.
2242 12744869 In contrast, encapsulation of same antigen in egg phosphatidyl-choline (egg PC) liposomes, just like antigen-incomplete Freund's adjuvant (IFA) complex, has inefficient access to the cytosolic pathway of MHC I-dependent antigen presentation and failed to generate antigen-specific CD8(+) cytotoxic T cell response.
2243 12744869 Furthermore, antigen entrapped in escheriosomes stimulates antigen-specific CD4(+) T cell proliferation and also enhances the level of IL-2, IFN-gamma and IL-4 in the immunized animals.
2244 12747757 Identification of a naturally processed NY-ESO-1 peptide recognized by CD8+ T cells in the context of HLA-B51.
2245 12747757 The assessment of spontaneous and vaccine-induced CD8+ T cell responses has been limited to a small number of known NY-ESO-1 epitopes presented by MHC class I alleles.
2246 12747757 Recently, a new method to monitor NY-ESO-1-specific CD8+ T cell responses was introduced that does not depend on the individual MHC class I status and on predefined peptide epitopes.
2247 12747757 Antigen-presenting cells transduced with recombinant adenoviral vectors encoding NY-ESO-1 were used to stimulate CD8+ selected NY-ESO-1-specific T cells.
2248 12747757 Using a modified approach we identified the NY-ESO-1 p94-102 peptide as being recognized by CD8+ T cells in the context of HLA- B51.
2249 12747757 NY-ESO-1 p94-102 specific CD8+ T cells recognized naturally processed NY-ESO-1 presented by HLA-B51+ monocyte-derived dendritic and tumor cells.
2250 12747757 Transfection of target cells with NY-ESO-1 combined with different HLA class I alleles confirmed that the NY-ESO-1 peptide was naturally processed and recognized by HLA-B51-restricted CD8+ T cell lines and clones.
2251 12747757 Identification of a naturally processed NY-ESO-1 peptide recognized by CD8+ T cells in the context of HLA-B51.
2252 12747757 The assessment of spontaneous and vaccine-induced CD8+ T cell responses has been limited to a small number of known NY-ESO-1 epitopes presented by MHC class I alleles.
2253 12747757 Recently, a new method to monitor NY-ESO-1-specific CD8+ T cell responses was introduced that does not depend on the individual MHC class I status and on predefined peptide epitopes.
2254 12747757 Antigen-presenting cells transduced with recombinant adenoviral vectors encoding NY-ESO-1 were used to stimulate CD8+ selected NY-ESO-1-specific T cells.
2255 12747757 Using a modified approach we identified the NY-ESO-1 p94-102 peptide as being recognized by CD8+ T cells in the context of HLA- B51.
2256 12747757 NY-ESO-1 p94-102 specific CD8+ T cells recognized naturally processed NY-ESO-1 presented by HLA-B51+ monocyte-derived dendritic and tumor cells.
2257 12747757 Transfection of target cells with NY-ESO-1 combined with different HLA class I alleles confirmed that the NY-ESO-1 peptide was naturally processed and recognized by HLA-B51-restricted CD8+ T cell lines and clones.
2258 12747757 Identification of a naturally processed NY-ESO-1 peptide recognized by CD8+ T cells in the context of HLA-B51.
2259 12747757 The assessment of spontaneous and vaccine-induced CD8+ T cell responses has been limited to a small number of known NY-ESO-1 epitopes presented by MHC class I alleles.
2260 12747757 Recently, a new method to monitor NY-ESO-1-specific CD8+ T cell responses was introduced that does not depend on the individual MHC class I status and on predefined peptide epitopes.
2261 12747757 Antigen-presenting cells transduced with recombinant adenoviral vectors encoding NY-ESO-1 were used to stimulate CD8+ selected NY-ESO-1-specific T cells.
2262 12747757 Using a modified approach we identified the NY-ESO-1 p94-102 peptide as being recognized by CD8+ T cells in the context of HLA- B51.
2263 12747757 NY-ESO-1 p94-102 specific CD8+ T cells recognized naturally processed NY-ESO-1 presented by HLA-B51+ monocyte-derived dendritic and tumor cells.
2264 12747757 Transfection of target cells with NY-ESO-1 combined with different HLA class I alleles confirmed that the NY-ESO-1 peptide was naturally processed and recognized by HLA-B51-restricted CD8+ T cell lines and clones.
2265 12748263 Control and clearance of a vaccine strain rely on the phagocyte oxidative burst, reactive nitrogen intermediates, inflammatory cytokines and CD4(+) TCR-alphabeta(+) T cells and are controlled by genes including NRAMP1 and MHC class II.
2266 12750257 The linkage of gamma-tubulin to E7-targeted antigen to centrosomal compartments, resulted in enhanced MHC class I presentation of E7, and led to a marked increase in the number of E7-specific CD8(+) T-cell precursors as well as a potent CD4-independent antitumor effect against an E7-expressing tumor cell line, TC-1.
2267 12750257 Our data suggest that the centrosome may be an important locus for MHC class I antigen processing and that targeting antigen to the centrosome can improve DNA vaccine potency.
2268 12750257 The linkage of gamma-tubulin to E7-targeted antigen to centrosomal compartments, resulted in enhanced MHC class I presentation of E7, and led to a marked increase in the number of E7-specific CD8(+) T-cell precursors as well as a potent CD4-independent antitumor effect against an E7-expressing tumor cell line, TC-1.
2269 12750257 Our data suggest that the centrosome may be an important locus for MHC class I antigen processing and that targeting antigen to the centrosome can improve DNA vaccine potency.
2270 12761131 Attenuated Yersinia pseudotuberculosis carrier vaccine for simultaneous antigen-specific CD4 and CD8 T-cell induction.
2271 12761131 In comparison to wild-type Yersinia, an attenuated Y. pseudotuberculosis yopK-null mutant strain hypertranslocates chimeric YopE/LLO into the cytosol of macrophages, resulting in enhanced major histocompatibility complex (MHC) class I-restricted antigen presentation of an LLO-derived CD8 T-cell epitope.
2272 12761131 Animals orally inoculated with recombinant Yersinia expressing translocated chimeric YopE/LLO revealed high numbers of gamma interferon-producing LLO-specific CD4 and CD8 T cells.
2273 12761131 For the first time, it is shown that cytosolic antigen display mediated by an extracellular bacterial carrier vaccine results in simultaneous CD4 and CD8 T-cell priming, conferring protection against an intracellular pathogen.
2274 12778480 The results indicate that immunization with MHC anchor-improved MUC1 glycopeptide libraries can effectively prime T helper cells and may induce long-term memory.
2275 12782590 Immune-splenic lymphocytes when stimulated in vitro with 3H1 or CEA, showed increased proliferative CD4(+) Th1 type T-cell response and secreted significantly high levels of Th1 cytokines [IFN-gamma, interleukin (IL)-2] and low levels of Th2 cytokines (IL-4, IL-10).
2276 12782590 This vaccine also induced MHC class I antigen-restricted CD8(+) T-cell responses.
2277 12782590 The up-regulation of activation markers CD69 and CD25 on CD8(+) CTLs correlated with antigen-specific strong CTL responses in vitro.
2278 12786997 Lack of association between transporter associated with antigen processing (TAP) and HLA-DM gene polymorphisms and antibody levels following measles vaccination.
2279 12786997 The transporter associated with antigen processing (TAP) and human leukocyte antigen-DM (HLA-DM) genes are involved in the antigen-processing pathway of both HLA class I and class II-restricted antigen presentation.
2280 12786997 We determined TAP1 and TAP2 allele types by polymerase chain reaction (PCR) amplification of specific alleles (PASA) and determined DM allele type by PCR amplification followed by direct sequencing of the polymorphic sites.
2281 12786997 In addition, we did not find an association between TAP (TAP1, P = 0.71; TAP2, P = 0.87) or DM (DMA, P = 0.42; DMB, P = 0.71) homozygosity and seronegativity to measles vaccine in this study group.
2282 12804136 Granulocyte-macrophage colony-stimulating factor gene-transduced tumor cells combined with tumor-derived gp96 inhibit tumor growth in mice.
2283 12804136 Granulocyte-macrophage colony-stimulating factor (GM-CSF)-based cancer cell vaccines have been shown to be potent inducers of antitumor immunity in several murine models, but the antitumor effects on established tumors have been minimal.
2284 12804136 Moreover, draining lymph nodes from mice immunized with irradiated LLC/GM cells and LLC-derived gp96 contained more migrating mature CD11c(+) cells (higher levels of CD86 and major histocompatibility complex [MHC] class II molecules) compared with those from any other immunization protocols.
2285 12804139 This phenotype was created by intratumoral injection of plasmid cDNAs coding for interferon gamma, MHC class II transactivator, and an antisense reverse gene construct (RGC) for a segment of the gene for Ii protein (-92,97).
2286 12806275 A glycine-alanine repeat domain inhibits antigen processing through the ubiquitin-proteasome pathway for presentation on human leukocyte antigen (HLA) class I molecules.
2287 12817030 We now demonstrate that one or more genes encoded within the MHC selectively censor the ability of H-2(b) mice to mount this conformation-dependent autoantibody response, while leaving T and B cell responses to linear MOG(Igd) epitopes intact.
2288 12818619 The latter DCs present processed antigenic molecules from the pathogens to competent alphabeta T cells together with special containers, such as class I, class II MHC and CD1 to generate specific cellular immunity.
2289 12824194 The increased immune response is attributed to trafficking of the antigen chimera to the major histocompatibility class II (MHC II) compartment where LAMP is colocalized with MHC II.
2290 12824194 Gag encoded with the translocon, transmembrane and cytoplasmic lysosomal membrane targeting sequences of LAMP, without the luminal domain, was poorly expressed, did not traffic to lysosomes or MHC II compartments of transfected cells, and elicited a limited immune response from DNA immunized mice.
2291 12824194 This LAMP/Gag chimera with the complete LAMP protein colocalized with endogenous MHC II of transfected cells and elicited strong cellular and humoral immune responses of immunized mice as compared with the response to DNA-encoding native Gag, with a 10-fold increase in CD4+ responses, a 4- to 5-fold increase in CD8+ T-cell responses, and antibody titers of >100,000.
2292 12824194 The increased immune response is attributed to trafficking of the antigen chimera to the major histocompatibility class II (MHC II) compartment where LAMP is colocalized with MHC II.
2293 12824194 Gag encoded with the translocon, transmembrane and cytoplasmic lysosomal membrane targeting sequences of LAMP, without the luminal domain, was poorly expressed, did not traffic to lysosomes or MHC II compartments of transfected cells, and elicited a limited immune response from DNA immunized mice.
2294 12824194 This LAMP/Gag chimera with the complete LAMP protein colocalized with endogenous MHC II of transfected cells and elicited strong cellular and humoral immune responses of immunized mice as compared with the response to DNA-encoding native Gag, with a 10-fold increase in CD4+ responses, a 4- to 5-fold increase in CD8+ T-cell responses, and antibody titers of >100,000.
2295 12824194 The increased immune response is attributed to trafficking of the antigen chimera to the major histocompatibility class II (MHC II) compartment where LAMP is colocalized with MHC II.
2296 12824194 Gag encoded with the translocon, transmembrane and cytoplasmic lysosomal membrane targeting sequences of LAMP, without the luminal domain, was poorly expressed, did not traffic to lysosomes or MHC II compartments of transfected cells, and elicited a limited immune response from DNA immunized mice.
2297 12824194 This LAMP/Gag chimera with the complete LAMP protein colocalized with endogenous MHC II of transfected cells and elicited strong cellular and humoral immune responses of immunized mice as compared with the response to DNA-encoding native Gag, with a 10-fold increase in CD4+ responses, a 4- to 5-fold increase in CD8+ T-cell responses, and antibody titers of >100,000.
2298 12824380 MHCPred implements robust statistical models for both Class I alleles (HLA-A*0101, HLA-A*0201, HLA-A*0202, HLA-A*0203, HLA-A*0206, HLA-A*0301, HLA-A*1101, HLA-A*3301, HLA-A*6801, HLA-A*6802 and HLA-B*3501) and Class II alleles (HLA-DRB*0401, HLA-DRB*0401 and HLA-DRB*0701).
2299 12825169 VZV immediate early protein 62 (IE62) is recognized by cytotoxic T cells from immune individuals, but no CD8(+) T cell epitopes have been defined for any VZV protein.
2300 12825169 CD8(+) T cell frequencies were assessed by cytokine flow cytometry (CFC), by use of synthetic-peptide pools corresponding to the IE62 sequence.
2301 12825169 IE62 peptide-specific CD8(+) T cells were below the threshold of detection, by direct CFC of either whole blood or peripheral blood mononuclear cells (PBMCs).
2302 12825169 Activated CD8(+)CD69(+) T cells that produced interferon-gamma were detectable after in vitro restimulation of PBMCs, and restricted epitopes were identified for HLA-A*0201-positive subjects.
2303 12838324 Parathyroid hormone-related protein (PTH-rP), a secreted protein produced by prostate carcinoma and other epithelial cancers, is considered a key agent for the development of bone metastases.
2304 12838324 We investigated the construct GC90/IRIV, composed of immunopotentiating reconstituted influenza virosomes (IRIV) containing PTH-rP gene plasmids (GC90), as a potential tool for human anticancer immunotherapy into humanised mice transgenic for HLA-A(*)02.01, the human-beta2 microglobulin, and the human CD8alpha molecule.
2305 12845773 Furthermore, a Major Histocompatibility Complex (MHC)-class-I-restricted T cell activation ELISPOT assay showed elevated interferon-gamma, interleukin-2, and interleukin-12 production in HA/SHIV 89.6 VLP-immunized mice, indicating that phenotypically mixed HA/SHIV 89.6 VLPs can enhance both humoral and cellular immune responses at multiple mucosal sites.
2306 12862419 Reconstitution of CD40 and CD80 in dendritic cells generated from blasts of patients with acute myeloid leukemia.
2307 12862419 DCs must express HLA class I/II molecules and the costimulatory molecules CD40, CD80 and CD86 to effectively activate T cells for the subsequent lysis of leukemic blasts.
2308 12862419 The sustained mRNA expression of LAAs such as PRAME, RHAMM or WT-1 proved that the AML-DCs originated from AML blasts.
2309 12862419 Compared with AML blasts, the expression of CD40, CD80, CD86 and HLA-DR was upregulated during DC culture to a median of 80-98% on AML-DCs.
2310 12862419 Expression of CD40, CD80 and CD83 remained lower on AML-DCs than on HV-DCs.
2311 12874227 Analysis of HLA-E peptide-binding specificity and contact residues in bound peptide required for recognition by CD94/NKG2.
2312 12874227 The MHC class Ib molecule HLA-E is the primary ligand for CD94/NKG2A-inhibitory receptors expressed on NK cells, and there is also evidence for TCR-mediated recognition of this molecule.
2313 12874227 Experiments with HLA-E tetramers bearing peptides substituted at nonanchor positions demonstrated that P5 and P8 are primary contact residues for interaction with CD94/NKG2 receptors.
2314 12874227 A conservative replacement of Arg for Lys at P5 completely abrogated binding to CD94/NKG2.
2315 12874227 Despite conservation of peptide-binding specificity in HLA-E and Qa-1, cross-species tetramer-staining experiments demonstrated that the interaction surfaces on CD94/NKG2 and the class Ib ligands have diverged between primates and rodents.
2316 12875522 There was increased expression of the HLA class I-B (p = 0.0002), HLA class II cluster of DMA, DMB, TAP1, TAP2 (p = 0.0007) and HLA-DR (p = 0.0001) genes, and decreased expression of HLA class I MICB molecule (p = 1), HLA class I-A (p = 0.9999) and major histocompatibility complex class III HSP 70 (p = 0.9999) genes on day 7 or day 14 postvaccination in seropositives compared with seronegatives.
2317 12882660 We attempted to identify HLA-A*3303-restricted CTL epitopes derived from relatively conserved proteins Pol, Gag, and Nef of HIV-1 clade B, using reverse immunogenetics.
2318 12883527 CD8+ T cells, NK cells and IFN-gamma are important for control of tumor with downregulated MHC class I expression by DNA vaccination.
2319 12883527 We developed an E7-expressing murine tumor model with downregulated MHC class I expression, TC-1 P3 (A15).
2320 12883527 We found that vaccination with DNA encoding E7 linked to Mycobacterial heat shock protein 70 (HSP70) generated a significant antitumor effect against TC-1 P3 (A15), while vaccination with E7/HSP70 vaccinia did not generate an appreciable antitumor effect.
2321 12883527 Lymphocyte depletion experiments revealed that both CD8+ T cells and NK cells were essential for the antitumor effect generated by E7/HSP70 DNA against TC-1 P3 (A15).
2322 12883527 Furthermore, tumor protection experiments using IFN-gamma knockout mice revealed that IFN-gamma was essential for the antitumor effect generated by E7/HSP70 DNA against TC-1 P3 (A15).
2323 12883527 Our results demonstrate that vaccination with E7/HSP70 DNA results in a significant antitumor effect against a neoplasm with downregulated MHC class I expression and the importance of CD8+ T cells, NK cells, and IFN-gamma in generating this antitumor effect.
2324 12883527 CD8+ T cells, NK cells and IFN-gamma are important for control of tumor with downregulated MHC class I expression by DNA vaccination.
2325 12883527 We developed an E7-expressing murine tumor model with downregulated MHC class I expression, TC-1 P3 (A15).
2326 12883527 We found that vaccination with DNA encoding E7 linked to Mycobacterial heat shock protein 70 (HSP70) generated a significant antitumor effect against TC-1 P3 (A15), while vaccination with E7/HSP70 vaccinia did not generate an appreciable antitumor effect.
2327 12883527 Lymphocyte depletion experiments revealed that both CD8+ T cells and NK cells were essential for the antitumor effect generated by E7/HSP70 DNA against TC-1 P3 (A15).
2328 12883527 Furthermore, tumor protection experiments using IFN-gamma knockout mice revealed that IFN-gamma was essential for the antitumor effect generated by E7/HSP70 DNA against TC-1 P3 (A15).
2329 12883527 Our results demonstrate that vaccination with E7/HSP70 DNA results in a significant antitumor effect against a neoplasm with downregulated MHC class I expression and the importance of CD8+ T cells, NK cells, and IFN-gamma in generating this antitumor effect.
2330 12883527 CD8+ T cells, NK cells and IFN-gamma are important for control of tumor with downregulated MHC class I expression by DNA vaccination.
2331 12883527 We developed an E7-expressing murine tumor model with downregulated MHC class I expression, TC-1 P3 (A15).
2332 12883527 We found that vaccination with DNA encoding E7 linked to Mycobacterial heat shock protein 70 (HSP70) generated a significant antitumor effect against TC-1 P3 (A15), while vaccination with E7/HSP70 vaccinia did not generate an appreciable antitumor effect.
2333 12883527 Lymphocyte depletion experiments revealed that both CD8+ T cells and NK cells were essential for the antitumor effect generated by E7/HSP70 DNA against TC-1 P3 (A15).
2334 12883527 Furthermore, tumor protection experiments using IFN-gamma knockout mice revealed that IFN-gamma was essential for the antitumor effect generated by E7/HSP70 DNA against TC-1 P3 (A15).
2335 12883527 Our results demonstrate that vaccination with E7/HSP70 DNA results in a significant antitumor effect against a neoplasm with downregulated MHC class I expression and the importance of CD8+ T cells, NK cells, and IFN-gamma in generating this antitumor effect.
2336 12894571 These problems emanate from the following mechanisms that the tumor cells are employing to avoid detection and destruction by the immune system: (i) Down-regulation of HLA class I expression on the surface of tumor cells; (ii) Down-regulation of tumor antigen expression or selection of negative tumor variants; (iii) Expression of naturally occurring altered peptide ligands by tumor cells; (iv) Lack of costimulatory molecules on tumors cells; (v) Production of immunosuppressive cytokines, such as TGF-beta and IL-10; (vi) Induction of lymphocyte apoptosis by tumor cells using the Fas/Fas L pathway; (vii) Down-regulation or absence of CD3 zeta (zeta) transcripts or protein in tumor-infiltrating lymphocytes (TIL), and others.
2337 12900767 The MHC Class II+/Ii- tumor cell phenotype is created by transfecting genes for either CIITA or IFN-gamma, and inhibiting induced Ii mRNA by an Ii reverse gene construct (Ii-RGC).
2338 12900767 Here we show that at 5 MOI (multiplicity of infection), recombinant adenoviruses with CIITA or IFN-gamma genes converted virtually all MC-38 colon adenocarcinoma cells and Renca renal carcinoma cells in culture to MHC Class II+/Ii+ cells.
2339 12900767 A single recombinant adenovirus with both genes for IFN-gamma and Ii-RGC (rAV/IFN-gamma/Ii-RGC) efficiently induced the MHC Class II+/Ii- phenotype.
2340 12900767 Injection of tumor nodules with rAV/Ii-RGC and rAV/CIITA/IFN-gamma combined with a suboptimal dose of rAV/IL-2 induced a potent antitumor immune response.
2341 12900767 The MHC Class II+/Ii- tumor cell phenotype is created by transfecting genes for either CIITA or IFN-gamma, and inhibiting induced Ii mRNA by an Ii reverse gene construct (Ii-RGC).
2342 12900767 Here we show that at 5 MOI (multiplicity of infection), recombinant adenoviruses with CIITA or IFN-gamma genes converted virtually all MC-38 colon adenocarcinoma cells and Renca renal carcinoma cells in culture to MHC Class II+/Ii+ cells.
2343 12900767 A single recombinant adenovirus with both genes for IFN-gamma and Ii-RGC (rAV/IFN-gamma/Ii-RGC) efficiently induced the MHC Class II+/Ii- phenotype.
2344 12900767 Injection of tumor nodules with rAV/Ii-RGC and rAV/CIITA/IFN-gamma combined with a suboptimal dose of rAV/IL-2 induced a potent antitumor immune response.
2345 12900767 The MHC Class II+/Ii- tumor cell phenotype is created by transfecting genes for either CIITA or IFN-gamma, and inhibiting induced Ii mRNA by an Ii reverse gene construct (Ii-RGC).
2346 12900767 Here we show that at 5 MOI (multiplicity of infection), recombinant adenoviruses with CIITA or IFN-gamma genes converted virtually all MC-38 colon adenocarcinoma cells and Renca renal carcinoma cells in culture to MHC Class II+/Ii+ cells.
2347 12900767 A single recombinant adenovirus with both genes for IFN-gamma and Ii-RGC (rAV/IFN-gamma/Ii-RGC) efficiently induced the MHC Class II+/Ii- phenotype.
2348 12900767 Injection of tumor nodules with rAV/Ii-RGC and rAV/CIITA/IFN-gamma combined with a suboptimal dose of rAV/IL-2 induced a potent antitumor immune response.
2349 12918057 MHC class I- and II-restricted peptide epitopes, antigenic proteins, viral constructs, mini-genes and whole tumor cells have been used either alone or combined with different cytokines (i.e., IL-2, IL-12, GM-CSF), adjuvants (incomplete Freund's adjuvant, montanide, QS21) or with dendritic cells to induce specific immune responses in vivo.
2350 12928377 CpG DNA induces a class II transactivator-independent increase in class II MHC by stabilizing class II MHC mRNA in B lymphocytes.
2351 12928425 Importantly, 4 of these 6 CTL lines reproducibly recognize and lyse autologous primary CTCL cells in MHC class I/CD8-dependent fashion.
2352 12939642 In addition, we tested the ability of rVV-gp100-infected iDC and mDC to present the HLA-A*0201-associated gp100:209-217 epitope (g209).
2353 12944986 We inserted the genes encoding the MHC class I-restricted antigenic epitope of chicken ovalbumin and tyrosinase-related protein 2 into the signal sequence of the interleukin-2 gene, replacing part of the signal sequence at different positions.
2354 12946436 Retrovirus-transfected bone marrow cells cultured with GMCSF and IL-4 for 7 days demonstrated 70-80% of DCs with high CD11c, CD80, CD86, and MHC class I (I-Kd) expression.
2355 12946436 Immunization of DCs encoding SSP2 gene resulted in identification of two K(d) restricted CTL epitopes and induction of IFN-gamma-secreting cytolytic CD8+ T cells.
2356 12951870 The illustrated clinical and experimental results demonstrate the strong relationship between the MHC class I antigen HLA-B27 and synovial CD8+ T cells with specificity for bacterial and possible self-antigen in SpA.
2357 12960136 Here, we show that Her-2/neu-specific CTLs induced in vitro using peptide-pulsed dendritic cells efficiently lyse primary ALL blasts constitutively expressing both Her-2/neu and human leukocyte antigen A2 in an antigen-specific and MHC-restricted manner.
2358 12960169 A genome-wide search using major histocompatibility complex (MHC) class I binding and proteosome cleavage site algorithms identified 101 influenza A PR8 virus-derived peptides as potential epitopes for CD8+ T cell recognition in the H-2b mouse.
2359 12963273 CD4+, CD8+, and gammadelta T cells were analyzed before and after immunization for BRSV-specific in vitro recall responses, as evaluated by CD25 upregulation measured by flow cytometry.
2360 12963273 Inactivated vaccine also primed each T cell population for significant antigen-driven CD25 upregulation, including responses by CD4+ and gammadelta T cells that were stronger and longer-lasting than those primed by MLV.
2361 12963273 In summary, the data indicate that balanced BRSV-specific T cell responses can be induced by inactivated, as well as modified-live, conventional vaccines, which may implicate an alternative pathway of MHC class I antigen presentation.
2362 12966437 An anti-MUC1-antibody-interleukin-2 fusion protein that activates resting NK cells to lysis of MUC1-positive tumour cells.
2363 12966437 In MUC1-positive tumours, MHC class I expression is frequently downregulated and MUC1-specific cytotoxic T cells (CTLs) are either not available or in a state of anergy allowing tumour growth without limitation by CTL control.
2364 12966437 To activate lymphocytes and natural killer (NK) cells, we here generated an anti-MUC1-scFv-IL2 fusion protein (C595scFv-Fc-IL2) that contains the C595 single-chain antibody for MUC1 binding, the human IgG1 CH2CH3 domain for protein dimerisation, and interleukin-2 (IL2) for activation of immunological effector cells.
2365 12972510 We identified two 10 amino acid peptides that elicited cytolytic T lymphocyte activity and interferon-gamma production by CD8+ T cells from HLA-A*0201+ healthy tuberculin reactors.
2366 12973032 The authors vaccinated 18 HLA A*0201+ patients with stage IV melanoma with CD34 HPC-derived DCs pulsed with six antigens: influenza matrix peptide (Flu-MP), KLH, and peptides derived from the four melanoma antigens: MART-1/Melan A, gp100, tyrosinase, and MAGE-3.
2367 12973032 A single DC vaccination was sufficient for induction of KLH-specific CD4 T-cell responses in five patients and Flu-MP-specific CD8 T-cell responses in eight patients.
2368 12973032 Thus, a single injection of CD34 HPC-derived DCs can lead to rapid immune response to CD4 epitopes or to melanoma antigens.
2369 12974795 The IFN-gamma release Elispot assay was employed to assess effector CD8+ T cells.
2370 12974795 In two A*0206+ donors with CD8+ T-cell response to the peptide, the CD8+ T-cell frequency assessed by specific binding of peptide HLA-A*0201 tetramer was 4.62% and 1.66%, respectively.
2371 14500478 Parent OM selectively up-regulated Toll-like receptor 4 (TLR4) mRNA expression and induced mo-DC maturation, as reflected by increased production of chemokines, proinflammatory cytokines, and CD83, CD80, CD86, CD40, and major histocompatibility complex (MHC) class II molecules.
2372 14500478 In contrast, LPS-deficient OM selectively up-regulated TLR2 mRNA expression and induced moderate increases in both cytokine production and expression of CD86 and MHC class II molecules.
2373 14500478 Parent OM selectively up-regulated Toll-like receptor 4 (TLR4) mRNA expression and induced mo-DC maturation, as reflected by increased production of chemokines, proinflammatory cytokines, and CD83, CD80, CD86, CD40, and major histocompatibility complex (MHC) class II molecules.
2374 14500478 In contrast, LPS-deficient OM selectively up-regulated TLR2 mRNA expression and induced moderate increases in both cytokine production and expression of CD86 and MHC class II molecules.
2375 14500642 HLA-A*0201-restricted CD8(+) T cells recognizing Ags expressed in human melanoma (melanoma Ag recognized by T cell-1 (MART-1)/melanoma Ag A (Melan-A)) or colon carcinoma (carcinoembryonic Ag (CEA)/epithelial cell adhesion molecule (EpCAM)) were triggered to release IFN-gamma and to mediate cytotoxic activity by HLA-A*0201-matched APCs pulsed with hsp96 purified from tumor cells expressing the relevant Ag.
2376 14500642 Immunization with autologous tumor-derived hsp96 induced a significant increase in the recognition of MART-1/Melan-A(27-35) in three of five HLA-A*0201 melanoma patients, and of CEA(571-579) and EpCAM(263-271) in two of five HLA-A*0201 colon carcinoma patients, respectively, as detected by ELISPOT and HLA/tetramer staining.
2377 14500642 HLA-A*0201-restricted CD8(+) T cells recognizing Ags expressed in human melanoma (melanoma Ag recognized by T cell-1 (MART-1)/melanoma Ag A (Melan-A)) or colon carcinoma (carcinoembryonic Ag (CEA)/epithelial cell adhesion molecule (EpCAM)) were triggered to release IFN-gamma and to mediate cytotoxic activity by HLA-A*0201-matched APCs pulsed with hsp96 purified from tumor cells expressing the relevant Ag.
2378 14500642 Immunization with autologous tumor-derived hsp96 induced a significant increase in the recognition of MART-1/Melan-A(27-35) in three of five HLA-A*0201 melanoma patients, and of CEA(571-579) and EpCAM(263-271) in two of five HLA-A*0201 colon carcinoma patients, respectively, as detected by ELISPOT and HLA/tetramer staining.
2379 14507304 We have investigated the carrier effect of glutathione-S-transferase (GST) in CBA and C57BL/6 mice which are high and low responder to EB200, respectively.
2380 14507304 Our results reveal that the MHC restriction in C57BL/6 mice was broken by the use of GST as a carrier.
2381 14512168 Since anti-Hu antibodies are not pathogenic, and oligoclonal CD8(+) T cells infiltrate neoplastic and nervous tissues, we examined MHC class I-restricted immunogenicity of human HuD.
2382 14512570 For the six most common HLA molecules (HLA-A2, -A3, -A11, -A24, -B7 superfamily, and -B8), an average of 10 (range, 3 to 15) HIV-1 epitopes were tested.
2383 14512570 CD8(+)-T-cell responses were evaluated according to the HLA class I molecules of the volunteers.
2384 14534734 Altered MHC class I antigen expression involves total loss, loss of haplotype, locus downregulation, allelic loss or downregulation, and combinations.
2385 14534734 Despite the MHC class I molecule deficiency and the resulting absence of the CD8+ T cell-mediated immunity, the tumour hosts were found to be capable of being immunized against MHC class I- tumours.
2386 14534734 Altered MHC class I antigen expression involves total loss, loss of haplotype, locus downregulation, allelic loss or downregulation, and combinations.
2387 14534734 Despite the MHC class I molecule deficiency and the resulting absence of the CD8+ T cell-mediated immunity, the tumour hosts were found to be capable of being immunized against MHC class I- tumours.
2388 14578870 CD4+ T cells targeting nonstructural HCV proteins were detected in proliferation assays by week 6 postinfection, but they failed to produce interferon gamma (IFN-gamma).
2389 14578870 HCV-specific CD4+ and CD8+ T cells with the ability to produce IFN-gamma appeared at week 8 when a rapid 10-fold reduction in plasma viremia was first observed.
2390 14578870 T cell lines targeting 3 CD4+ T cell epitopes and 1 CD8+ T cell epitope were derived from liver and their Patr major histocompatibility complex (MHC) restriction elements were identified.
2391 14578870 In conclusion, the characterization of the HCV epitopes and MHC class II restriction elements described here will facilitate a detailed comparison of CD4+ T cell function in animals with resolved and persistent infections.
2392 14578870 CD4+ T cells targeting nonstructural HCV proteins were detected in proliferation assays by week 6 postinfection, but they failed to produce interferon gamma (IFN-gamma).
2393 14578870 HCV-specific CD4+ and CD8+ T cells with the ability to produce IFN-gamma appeared at week 8 when a rapid 10-fold reduction in plasma viremia was first observed.
2394 14578870 T cell lines targeting 3 CD4+ T cell epitopes and 1 CD8+ T cell epitope were derived from liver and their Patr major histocompatibility complex (MHC) restriction elements were identified.
2395 14578870 In conclusion, the characterization of the HCV epitopes and MHC class II restriction elements described here will facilitate a detailed comparison of CD4+ T cell function in animals with resolved and persistent infections.
2396 14579264 Although cytotoxic T lymphocyte (CTL)-directed epitopes binding to human histocompatibility leukocyte antigen (HLA)-A molecules have been well characterized, those binding to HLA-B molecules have not, largely due to their large diversity.
2397 14579264 In this study we report a unique cancer antigen gene, tentatively named Testin-related gene (TRG), which encodes CTL-directed epitopes on the HLA-B52 molecules most frequently expressed in Asians.
2398 14579264 TRG is located in an intron of the putative tumor suppressor gene Testin in the common fragile site 7G region at 7q31.2.
2399 14581345 We therefore sought to identify promiscuous Th epitopes in hTERT, which can be presented by more than one MHC class II allele.
2400 14581345 Each of 10 peptides derived from hTERT that were predicted to bind to MHC class II molecules was found to be able to induce primary human T-cell responses in vitro.
2401 14581345 We then established CD4(+) T-cell clones specific for these peptides and found that only hTERT(766) (LTDLQPYMRQFVAHL)-specific CD4(+) Th cells were effective in recognizing naturally processed hTERT antigen.
2402 14581345 We further found that the naturally processed epitopes hTERT(766) and hTERT(672) (which was identified previously) were promiscuous and capable of inducing CD4(+) T-cell responses in the context of several commonly found HLA-DR alleles, including DR1, DR7, and DR15 for hTERT(672), and DR4, DR11, and DR15 for hTERT(766).
2403 14581345 We therefore sought to identify promiscuous Th epitopes in hTERT, which can be presented by more than one MHC class II allele.
2404 14581345 Each of 10 peptides derived from hTERT that were predicted to bind to MHC class II molecules was found to be able to induce primary human T-cell responses in vitro.
2405 14581345 We then established CD4(+) T-cell clones specific for these peptides and found that only hTERT(766) (LTDLQPYMRQFVAHL)-specific CD4(+) Th cells were effective in recognizing naturally processed hTERT antigen.
2406 14581345 We further found that the naturally processed epitopes hTERT(766) and hTERT(672) (which was identified previously) were promiscuous and capable of inducing CD4(+) T-cell responses in the context of several commonly found HLA-DR alleles, including DR1, DR7, and DR15 for hTERT(672), and DR4, DR11, and DR15 for hTERT(766).
2407 14583622 The HIV-1 envelope glycoprotein gp160 induces a strong specific CTL response restricted by several human and murine MHC class I molecules, including H-2Dd.
2408 14604955 Antibody-targeted MHC complex-directed expansion of HIV-1- and KSHV-specific CD8+ lymphocytes: a new approach to therapeutic vaccination.
2409 14604955 These expanded cells have an effector phenotype that includes the ability to produce interferon-gamma and CD45Ra+/CD69+ staining.
2410 14607868 A well-characterized subclass of these NKT cells expresses biased TCR and recognizes glycolipids such as alpha-galactoceramide, which is found naturally only in marine sponges and presented by the cell surface glycoprotein CD1d.
2411 14607868 Observing high frequencies of CD4 and CD8 coreceptor expression in human CD56+ T cells, we examined the potential role of major histocompatibility complex (MHC) class II molecules in the activation of these cells.
2412 14607868 Activation of mononuclear cells with bacterial superantigens presented by MHC class II molecules resulted in increased frequency of CD56+ T cells.
2413 14607868 Primarily, CD4+ cells within the CD56+-T-cell population responded to the bacterial superantigens, and cytokine expression profiles were Th1-like.
2414 14607868 Collectively, our data suggest that a significant number of CD56+ T cells recognize pathogen-associated ligands in association with MHC class II molecules.
2415 14607868 A well-characterized subclass of these NKT cells expresses biased TCR and recognizes glycolipids such as alpha-galactoceramide, which is found naturally only in marine sponges and presented by the cell surface glycoprotein CD1d.
2416 14607868 Observing high frequencies of CD4 and CD8 coreceptor expression in human CD56+ T cells, we examined the potential role of major histocompatibility complex (MHC) class II molecules in the activation of these cells.
2417 14607868 Activation of mononuclear cells with bacterial superantigens presented by MHC class II molecules resulted in increased frequency of CD56+ T cells.
2418 14607868 Primarily, CD4+ cells within the CD56+-T-cell population responded to the bacterial superantigens, and cytokine expression profiles were Th1-like.
2419 14607868 Collectively, our data suggest that a significant number of CD56+ T cells recognize pathogen-associated ligands in association with MHC class II molecules.
2420 14607868 A well-characterized subclass of these NKT cells expresses biased TCR and recognizes glycolipids such as alpha-galactoceramide, which is found naturally only in marine sponges and presented by the cell surface glycoprotein CD1d.
2421 14607868 Observing high frequencies of CD4 and CD8 coreceptor expression in human CD56+ T cells, we examined the potential role of major histocompatibility complex (MHC) class II molecules in the activation of these cells.
2422 14607868 Activation of mononuclear cells with bacterial superantigens presented by MHC class II molecules resulted in increased frequency of CD56+ T cells.
2423 14607868 Primarily, CD4+ cells within the CD56+-T-cell population responded to the bacterial superantigens, and cytokine expression profiles were Th1-like.
2424 14607868 Collectively, our data suggest that a significant number of CD56+ T cells recognize pathogen-associated ligands in association with MHC class II molecules.
2425 14611699 These data, together with information for other mouse strains, demonstrate that MHC (human and murine) and non-MHC genes contribute to the outcome of TSHR-DNA vaccination and indicate the potential value of DR3 transgenic mice for dissecting immune responses to the TSHR.
2426 14615150 The T-cell lines, primed by the recombinant AdVCEA-infected DCs in vitro, not only recognized CEA peptide-loaded target cells but also CEA-expressing tumor cell lines in a human leukocyte antigen (HLA) class I-restricted manner.
2427 14615150 Cytotoxic activity toward target cells was found to be mediated primarily by CD8(+) T-cells, although both CD8(+) cells and CD4(+) cells were able to lyse CEA peptide-loaded target cells.
2428 14629622 However, an increase in the levels of mRNAs coding for B7-1, transforming growth factor (TGF)-beta and major histocompatibility complex (MHC)-II was detected in the lungs after FHA administration.
2429 14629978 We have exemplified our method with a model for peptides binding to the common human MHC molecule HLA-B*3501.
2430 14630810 These CTLs secreted interferon-gamma (IFN-gamma) and killed targets in an MHC-restricted fashion.
2431 14632664 RNA samples from stimulated and unstimulated chicken thymocytes were assayed for messenger RNA encoding the cytokines interleukin-1beta (IL-1beta), IL-2, interferon-alpha (IFN-alpha), IFN-beta, IFN-gamma and transforming growth factor-beta4 (TGF-beta4), and also components of the major histocompatibility complex (MHC), beta2-microglobulin (beta2M) and the MHC class I alpha-chain (MHC IA).
2432 14632664 Mitogen stimulation of embryonic day 18 and day 1 post-hatch thymocytes induced up-regulation of IFN-gamma, IL-1beta and TGF-beta transcripts, and down-regulation of IFN-alpha, IFN-beta and IL-2 transcripts, with a higher induction of IFN-gamma, IL-1beta and TGF-beta transcripts in more immature T-cell-receptor-negative (TCR-) than TCR+ (TCR1+, TCR2+, or TCR3+) subsets.
2433 14632664 Thymocytes from embryonic day 14 chicks responded to mitogen with a short burst of unsustained proliferation, and transcriptional down-regulation of the cytokines IL-2, IL-1beta, IFN-alpha, IFN-beta and IFN-gamma.
2434 14632664 Transcripts encoding TGF-beta and type I interferons (IFN-alpha and IFN-beta) were constitutively expressed at high levels in very early thymocytes at embryonic day 14.
2435 14633722 We reported previously that a 16-amino acid peptide analogue derived from pigeon cytochrome c can bind broad ranges of MHC class II types and activate helper T cells in mice.
2436 14633722 Furthermore, immunofluorescent study of the inoculated tumors revealed increased accumulation of both CD4- and CD8-positive T cells producing IFN-gamma in the tumor only by this vaccine protocol.
2437 14634146 We previously described HLA-B35-restricted melanoma tumor-infiltrating lymphocyte responses to frequently expressed melanoma-associated Ags: tyrosinase, Melan-A/MART-1, gp100, MAGE-A3/MAGE-A6, and NY-ESO-1.
2438 14634146 In particular, the HLA-B35-restricted Melan-A epitope is mimicked by the peptide 26-35, already known as the most immunodominant melanoma epitope in the HLA-A*0201 context.
2439 14645154 In IL-10(-/-) mice, inflammation of the vaccination site was increased with larger numbers of IL-12p40(+), MHC II(+) and CD86(+) cells in the dermal exudate, and was associated with elevated levels of skin-derived IL-12p40 and IL-1beta.
2440 14645154 Moreover, such mice had increased numbers of CD4(+) sdLN cells that were CD25(+), CD28(+) or CD152(+) and accessory cells that were CD40(+) or MHC II(+).
2441 14645154 Finally, the secretion of IFN-gamma (and IL-12p40) by in vitro cultured sdLN cells was substantially raised in IL-10(-/-) mice, but much reduced in IL-12p40(-/-) mice, resulting in the development of highly polarized T(h)1 and T(h)2 cytokine profiles in the two groups of mice respectively.
2442 14662894 Detailed analysis of two monkeys revealed CD8(+) T cell responses to several peptide epitopes of Gag not previously described, at least two of which are restricted by MHC class I alleles not currently identified.
2443 14670336 Several immunomodulatory functions have been reported for Nef, including down-regulation of CD4 and class I MHC in T-lymphocytes, and the ability to enhance viral transmission from macrophages and dendritic cells (DC) to T-lymphocytes.
2444 14670336 In this study, HIV-1 (SF2 strain) Nef was expressed in human monocyte-derived dendritic cells, using an adenovirus based delivery system.
2445 14670336 Nef expression resulted in decreased CD4 levels, but no change to class I MHC, and no impairment in the ability of DC to stimulate recall PPD responses, mixed leukocyte responses, or hepatitis B-specific CD8 responses.
2446 14670336 The adenovirus vector itself stimulated a strong recall CD4 response in all individuals tested, and also induced up-regulation of class I MHC, CD86 and CD40 on the dendritic cell surface.
2447 14670336 Several immunomodulatory functions have been reported for Nef, including down-regulation of CD4 and class I MHC in T-lymphocytes, and the ability to enhance viral transmission from macrophages and dendritic cells (DC) to T-lymphocytes.
2448 14670336 In this study, HIV-1 (SF2 strain) Nef was expressed in human monocyte-derived dendritic cells, using an adenovirus based delivery system.
2449 14670336 Nef expression resulted in decreased CD4 levels, but no change to class I MHC, and no impairment in the ability of DC to stimulate recall PPD responses, mixed leukocyte responses, or hepatitis B-specific CD8 responses.
2450 14670336 The adenovirus vector itself stimulated a strong recall CD4 response in all individuals tested, and also induced up-regulation of class I MHC, CD86 and CD40 on the dendritic cell surface.
2451 14670336 Several immunomodulatory functions have been reported for Nef, including down-regulation of CD4 and class I MHC in T-lymphocytes, and the ability to enhance viral transmission from macrophages and dendritic cells (DC) to T-lymphocytes.
2452 14670336 In this study, HIV-1 (SF2 strain) Nef was expressed in human monocyte-derived dendritic cells, using an adenovirus based delivery system.
2453 14670336 Nef expression resulted in decreased CD4 levels, but no change to class I MHC, and no impairment in the ability of DC to stimulate recall PPD responses, mixed leukocyte responses, or hepatitis B-specific CD8 responses.
2454 14670336 The adenovirus vector itself stimulated a strong recall CD4 response in all individuals tested, and also induced up-regulation of class I MHC, CD86 and CD40 on the dendritic cell surface.
2455 14673108 Herein, we report that Ebola VLPs (eVLPs) were immunogenic in vitro as eVLPs matured and activated mouse bone marrow-derived dendritic cells, assessed by increases in cell-surface markers CD40, CD80, CD86, and MHC class I and II and secretion of IL-6, IL-10, macrophage inflammatory protein (MIP)-1alpha, and tumor necrosis factor alpha by the dendritic cells.
2456 14673108 Further, vaccinating mice with eVLPs activated CD4+ and CD8+ T cells, as well as CD19+ B cells.
2457 14676113 T-cell responses to HLA-A*0201 immunodominant peptides derived from alpha-fetoprotein in patients with hepatocellular cancer.
2458 14676632 Herein, we report the induction of high frequencies of circulating CD8+ T cells (4.8% to 38.1%) directed against the native gp100:209-217 peptide derived from the gp100 melanoma-melanocyte tumor antigen in five HLA-A*0201 patients at high risk of recurrence of melanoma after multiple courses of immunization with modified gp100:209-217(210M) peptide in IFA.
2459 14677925 Identification of an HLA-A*02 restricted immunogenic peptide derived from the cancer testis antigen HOM-MEL-40/SSX2.
2460 14677925 HOM-MEL-40/SSX2 is a SEREX-defined cancer testis antigen with frequent expression in various human neoplasms.
2461 14677925 To search for HLA-A*0201 restricted peptides that induce HOM-MEL-40/SSX2-specific CD8+ responses in breast cancer patients, we used the SYFPEITHI algorithm to identify three HOM-MEL-40/SSX2-derived nonamers with high binding affinity for HLA-A*0201, which has a prevalence of 40% in the Caucasian population.
2462 14677925 The natural processing and presentation of p103-111 was demonstrated by the recognition of the HOM-MEL-40/SSX2 positive cell line SK-MEL-37 and of COS7/A2 cells transfected with HOM-MEL-40/SSX2 by p103-111 specific CD8+ cells.
2463 14677925 No correlation was found between CD8+ T-cell responses against p103-111 and anti-HOM-MEL-40/SSX2 antibody titers in the serum of patients, suggesting that CD8+ and B-cell responses against HOM-MEL-40/SSX2 are regulated independently. p103-111 holds promise as a broadly applicable peptide vaccine for patients with HOM-MEL-40/SSX2 positive neoplasms.
2464 14677925 Identification of an HLA-A*02 restricted immunogenic peptide derived from the cancer testis antigen HOM-MEL-40/SSX2.
2465 14677925 HOM-MEL-40/SSX2 is a SEREX-defined cancer testis antigen with frequent expression in various human neoplasms.
2466 14677925 To search for HLA-A*0201 restricted peptides that induce HOM-MEL-40/SSX2-specific CD8+ responses in breast cancer patients, we used the SYFPEITHI algorithm to identify three HOM-MEL-40/SSX2-derived nonamers with high binding affinity for HLA-A*0201, which has a prevalence of 40% in the Caucasian population.
2467 14677925 The natural processing and presentation of p103-111 was demonstrated by the recognition of the HOM-MEL-40/SSX2 positive cell line SK-MEL-37 and of COS7/A2 cells transfected with HOM-MEL-40/SSX2 by p103-111 specific CD8+ cells.
2468 14677925 No correlation was found between CD8+ T-cell responses against p103-111 and anti-HOM-MEL-40/SSX2 antibody titers in the serum of patients, suggesting that CD8+ and B-cell responses against HOM-MEL-40/SSX2 are regulated independently. p103-111 holds promise as a broadly applicable peptide vaccine for patients with HOM-MEL-40/SSX2 positive neoplasms.
2469 14688321 Fully functional HLA B27-restricted CD4+ as well as CD8+ T cell responses in TCR transgenic mice.
2470 14688321 Surprisingly, HLA B27 supported CD4+ as well as CD8+ T cell responses in vivo and in vitro.
2471 14688321 Further, HLA B27-restricted CD4+ T cells were capable of differentiation into a range of Th1 and Th2 T cell subsets with normal patterns of cytokine expression.
2472 14688321 The existence of CD4+ MHC class I-restricted T cells has significant implications for immune regulation in autoimmunity and, in particular, in HLA B27-associated arthritis.
2473 14694109 Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma, a high-incidence tumor in southern China, expresses a limited set of EBV proteins, including the nuclear antigen EBNA1, an abundant source of HLA class II-restricted CD4(+) T-cell epitopes, and the latent membrane protein LMP2, a source of subdominant CD8(+) T-cell epitopes presented by HLA class I alleles common in the Chinese population.
2474 14694109 We used appropriately modified gene sequences from a Chinese EBV strain to generate a modified vaccinia virus Ankara recombinant, MVA-EL, expressing the CD4 epitope-rich C-terminal domain of EBNA1 fused to full-length LMP2.
2475 14694109 The endogenously expressed fusion protein EL is efficiently processed via the HLA class I pathway, and MVA-EL-infected dendritic cells selectively reactivate LMP2-specific CD8(+) memory T-cell responses from immune donors in vitro.
2476 14694109 Given its immunogenicity to both CD4(+) and CD8(+) T cells, MVA-EL has potential as a therapeutic vaccine in the context of nasopharyngeal carcinoma.
2477 14694109 Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma, a high-incidence tumor in southern China, expresses a limited set of EBV proteins, including the nuclear antigen EBNA1, an abundant source of HLA class II-restricted CD4(+) T-cell epitopes, and the latent membrane protein LMP2, a source of subdominant CD8(+) T-cell epitopes presented by HLA class I alleles common in the Chinese population.
2478 14694109 We used appropriately modified gene sequences from a Chinese EBV strain to generate a modified vaccinia virus Ankara recombinant, MVA-EL, expressing the CD4 epitope-rich C-terminal domain of EBNA1 fused to full-length LMP2.
2479 14694109 The endogenously expressed fusion protein EL is efficiently processed via the HLA class I pathway, and MVA-EL-infected dendritic cells selectively reactivate LMP2-specific CD8(+) memory T-cell responses from immune donors in vitro.
2480 14694109 Given its immunogenicity to both CD4(+) and CD8(+) T cells, MVA-EL has potential as a therapeutic vaccine in the context of nasopharyngeal carcinoma.
2481 14695218 MICA/NKG2D-mediated immunogene therapy of experimental gliomas.
2482 14695218 Tumor cells expressing ligands of the activating immunoreceptor NKG2D stimulate tumor immunity mediated by natural killer (NK), gammadelta T, and CD8(+) T cells.
2483 14695218 We report that human glioma cells express the NKG2D ligands MICA, MICB, and members of the UL16-binding protein family constitutively.
2484 14695218 However, glioma cells resist NK cell cytolysis because of high MHC class I antigen expression.
2485 14712489 Inducible Hsp70 as target of anticancer immunotherapy: Identification of HLA-A*0201-restricted epitopes.
2486 14712489 We selected the p391 and p393 peptides from the sequence of the human inducible Hsp70 that had a high affinity for HLA-A*0201.
2487 14712489 These peptides were able to trigger a CTL response in vivo in HLA-A*0201-transgenic HHD mice and in vitro in HLA-A*0201+ healthy donors. p391- and p393-specific human and murine CTL recognized human tumor cells overexpressing Hsp70 in a HLA-A*0201-restricted manner.
2488 14712489 Tetramer analysis of TILs showed that these Hsp70 epitopes are targets of an immune response in many HLA-A*0201+ breast cancer patients.
2489 14712489 Inducible Hsp70 as target of anticancer immunotherapy: Identification of HLA-A*0201-restricted epitopes.
2490 14712489 We selected the p391 and p393 peptides from the sequence of the human inducible Hsp70 that had a high affinity for HLA-A*0201.
2491 14712489 These peptides were able to trigger a CTL response in vivo in HLA-A*0201-transgenic HHD mice and in vitro in HLA-A*0201+ healthy donors. p391- and p393-specific human and murine CTL recognized human tumor cells overexpressing Hsp70 in a HLA-A*0201-restricted manner.
2492 14712489 Tetramer analysis of TILs showed that these Hsp70 epitopes are targets of an immune response in many HLA-A*0201+ breast cancer patients.
2493 14712489 Inducible Hsp70 as target of anticancer immunotherapy: Identification of HLA-A*0201-restricted epitopes.
2494 14712489 We selected the p391 and p393 peptides from the sequence of the human inducible Hsp70 that had a high affinity for HLA-A*0201.
2495 14712489 These peptides were able to trigger a CTL response in vivo in HLA-A*0201-transgenic HHD mice and in vitro in HLA-A*0201+ healthy donors. p391- and p393-specific human and murine CTL recognized human tumor cells overexpressing Hsp70 in a HLA-A*0201-restricted manner.
2496 14712489 Tetramer analysis of TILs showed that these Hsp70 epitopes are targets of an immune response in many HLA-A*0201+ breast cancer patients.
2497 14712489 Inducible Hsp70 as target of anticancer immunotherapy: Identification of HLA-A*0201-restricted epitopes.
2498 14712489 We selected the p391 and p393 peptides from the sequence of the human inducible Hsp70 that had a high affinity for HLA-A*0201.
2499 14712489 These peptides were able to trigger a CTL response in vivo in HLA-A*0201-transgenic HHD mice and in vitro in HLA-A*0201+ healthy donors. p391- and p393-specific human and murine CTL recognized human tumor cells overexpressing Hsp70 in a HLA-A*0201-restricted manner.
2500 14712489 Tetramer analysis of TILs showed that these Hsp70 epitopes are targets of an immune response in many HLA-A*0201+ breast cancer patients.
2501 14730400 MHC class II and CD80 tumor cell-based vaccines are potent activators of type 1 CD4+ T lymphocytes provided they do not coexpress invariant chain.
2502 14730400 MHC class II(+)CD80+ vaccine cells were transfected with hen eggwhite lysozyme targeted to the cytosol, nuclei, mitochondria, or endoplasmic reticulum, and used as antigen-presenting cells to activate I-Ak-restricted, lysozyme-specific CD4+ 3A9 transgenic T cells.
2503 14730400 Regardless of the cellular location of lysozyme, the vaccines stimulated release of high levels of IFN-gamma and IL-2.
2504 14730400 If the vaccines coexpressed the MHC class II accessory molecule invariant chain, then IFN-gamma and IL-2 release was significantly reduced.
2505 14730400 These studies demonstrate that in the absence of invariant chain the MHC class II and CD80 tumor cell vaccines (1) function as antigen-presenting cells to activate naïve, tumor-specific CD4+ cells to endogenously synthesized tumor antigens; (2) polarize the activated CD4+ T cells toward a type 1 response; and (3) present epitopes derived from varied subcellular locales.
2506 14734741 We describe in this study a predominant T cell population localized within two murine tumors that is characterized by expression of apoptotic markers and TCRalphabeta/CD3, but not CD4, CD8, or NK-associated markers.
2507 14734741 Adoptive transfer into s.c. tumors demonstrated that naive CD8(+) T cells were highly susceptible to becoming DN TIL, and local supplementation of tumors with nontumor Ag-bearing MHC class I-expressing fibroblasts decreased both this susceptibility and endogenous DN TIL levels.
2508 14738452 Major histocompatibility complex (MHC) class II-dependent antigens not only activate CD4+ T helper (Th) cells, but also cytolytic T lymphocytes and effector cells of the innate immune system.
2509 14741164 Taken together these findings indicate that IRIV are endowed with a high adjuvant capacity for HLA class I restricted CTL induction, largely attributable to their ability to antigenically stimulate CD4+ T cells.
2510 14748438 For these purposes, we have used two oncogenic cell lines induced independently by co-transfection of murine H-2b cells with E61E7 HPV16 and activated Ha-ras oncogenes, the tumours TC-1 (MHC class I+, HPV16 E7+) and E7+).
2511 14748438 Preimmunization with the MHC class I+ tumour did not protect against a subsequent challenge with the MHC class I- tumour and vice versa; however, immunization with the TC-1 tumour could protect syngeneic mice against the TC-1 tumour challenge and, similarly, immunization with the MK16/1/IIIABC tumour could protect mice against the MK16/1/IIIABC tumour challenge.
2512 14748438 For these purposes, we have used two oncogenic cell lines induced independently by co-transfection of murine H-2b cells with E61E7 HPV16 and activated Ha-ras oncogenes, the tumours TC-1 (MHC class I+, HPV16 E7+) and E7+).
2513 14748438 Preimmunization with the MHC class I+ tumour did not protect against a subsequent challenge with the MHC class I- tumour and vice versa; however, immunization with the TC-1 tumour could protect syngeneic mice against the TC-1 tumour challenge and, similarly, immunization with the MK16/1/IIIABC tumour could protect mice against the MK16/1/IIIABC tumour challenge.
2514 14755339 We addressed this question by evaluating in HLA-A*0201-transgenic HHD mice the antitumor vaccination efficacy of high- and low-affinity epitopes from the naturally expressed murine telomerase reverse transcriptase (mTERT).
2515 14760090 gp100(209-2M) peptide immunization of human lymphocyte antigen-A2+ stage I-III melanoma patients induces significant increase in antigen-specific effector and long-term memory CD8+ T cells.
2516 14760090 Ex vivo IFN-gamma cytokine flow cytometry analysis of postvaccine PBMCs after brief gp100(209-2M) in vitro activation showed that for all of the patients studied tetramer(+) CD8(+) T cells produced IFN-gamma; however, some patients had significant numbers of tetramer(+) IFN-gamma(-) CD8(+)T cells suggesting functional anergy.
2517 14760090 Additionally, 8 day gp100(209-2M) in vitro stimulation (IVS) of pre- and postvaccine PBMCs resulted in significant expansion of tetramer(+) CD8(+) T cells from postvaccine cells for 34 patients, and these IVS tetramer(+) CD8(+) T cells were functionally responsive by IFN-gamma cytokine flow cytometry analysis after restimulation with either native or modified gp100 peptide.
2518 14760090 Overall, this report demonstrates that after vaccination with a MHC class I-restricted melanoma peptide, resected nonmetastatic melanoma patients can mount a significant antigen-specific CD8(+) T-cell immune response with a functionally intact memory component.
2519 14764679 However, we showed in part I that exosomes are efficient to promote primary MHC class I-restricted effector CD8(+) T cell responses only when transferred onto mature DC in vivo.
2520 14764679 In this work, we bring evidence that among the clinically available reagents, Toll-like receptor 3 and 9 ligands are elective adjuvants capable of triggering efficient MHC-restricted CD8(+) T cell responses when combined to exosomes.
2521 14764714 We found that OMPC and Hib-OMPC engaged human Toll-like receptor 2 (TLR2) expressed in human embryonic kidney (HEK) cells, inducing IL-8 production, and engaged mouse TLR2 on bone marrow-derived dendritic cells, inducing TNF release.
2522 14764714 Engagement of TLR2 by Hib-OMPC was MyD88 dependent, as Hib-OMPC-induced TNF production was ablated in MyD88 knockout (KO) mice.
2523 14764714 Splenocytes from OMPC-immunized TLR2 KO mice also produced significantly less IL-6 and TNF-alpha than those from wild-type mice.
2524 14764714 Hib-OMPC is unique among glycoconjugate vaccines by engaging TLR2, and the ability of Hib-OMPC to elicit protective levels of Abs after one dose may be related to TLR2-mediated induction and regulation of cytokines produced by T cells and macrophages in addition to the peptide/MHC II-dependent recruitment of T cell help commonly afforded by carrier proteins.
2525 14871853 Using a novel approach that combines DNA chip analysis of tumor samples with isolation of peptides on the surface of tumor cells, a HLA-A*0201-binding peptide derived from the adipophilin protein was identified.
2526 14871853 To further analyze the possible use of this peptide in immunotherapies of human malignancies, we induced adipophilin-specific CTLs using peripheral blood mononuclear cells and DCs from HLA-A*0201-positive patients with chronic lymphatic leukemia and plasma cell leukemia.
2527 14871853 Using a novel approach that combines DNA chip analysis of tumor samples with isolation of peptides on the surface of tumor cells, a HLA-A*0201-binding peptide derived from the adipophilin protein was identified.
2528 14871853 To further analyze the possible use of this peptide in immunotherapies of human malignancies, we induced adipophilin-specific CTLs using peripheral blood mononuclear cells and DCs from HLA-A*0201-positive patients with chronic lymphatic leukemia and plasma cell leukemia.
2529 14971031 Dendritic cells generated in the presence of GM-CSF plus IL-15 prime potent CD8+ Tc1 responses in vivo.
2530 14971031 DC progenitors can be stimulated to differentiate into immature DC by various growth factors, including GM-CSF and IL-4.
2531 14971031 Here we show that IL-15, in combination with GM-CSF, is a growth factor for murine DC.
2532 14971031 Murine bone marrow cells, depleted of T cells, B cells, I-A+ cells and Gr-1+ granulocytes, and cultured in the presence of GM-CSF plus IL-15 (IL-15 DC), yielded DC expressing high levels of CD11c and MHC class II molecules, as well as CD11b.
2533 14971031 These cells expressed significant levels of CD40, CD80 and CD86, and could stimulate allogeneic CD4+ T cells efficiently.
2534 14971031 Interestingly, IL-15 DC were far superior to DC generated with GM-CSF plus IL-4 in stimulating allogeneic CD8+ T cells in vitro.
2535 14971031 Consistent with this, IL-15 DC induced much more potent antigen-specific CD8+ T cell responses with high levels of Th1 cytokines in vivo, compared to DC generated with GM-CSF plus IL-4, or with GM-CSF plus TGF-beta, or with GM-CSF alone.
2536 14971031 Together, these data suggest that IL-15 promotes the development of DC, which induce potent Th1 and Tc1 responses in vivo.
2537 14973049 The EBV-encoded latent membrane proteins (LMP1 and LMP2), which are expressed in various EBV-associated malignancies have been proposed as a potential target for CTL-based therapy.
2538 14973049 Here we have developed a replication- incompetent adenoviral vaccine that encodes multiple HLA class I-restricted CTL epitopes from LMP1 and LMP2 as a polyepitope.
2539 14973049 These expanded T cells displayed strong lysis of autologous target cells sensitized with LMP1 and/or LMP2 CTL epitopes.
2540 14991620 In vitro stimulation of immature murine DC with MALP-2 resulted in the induction of maturation with up-regulated expression of MHC class II, costimulatory (CD80, CD86) and adhesion (CD40, CD54) molecules.
2541 14991620 MALP-2 also enhances the secretion of cytokines (IL-1alpha, IL-6 and IL-12), and increases DC stimulatory activity on naive and antigen-specific T cells.
2542 14991620 Further studies demonstrated that MALP-2 treatment of DC results in a dose-dependent shift from the protein pattern of proteasomes to immunoproteasomes (up-regulation of LMP2, LMP7 and MECL1), which correlates with an increased proteolytic activity.
2543 14996751 We demonstrated previously that the vaccine cells present tumor peptides via the endogenous antigen presentation pathway to activate CD4(+) and CD8(+) T cells.
2544 14996751 To obtain MHC class II(+)CD80(+)Ii(-) human tumor cells, we developed retroviruses encoding HLA-DR and CD80.
2545 14996751 SUM159PT mammary carcinoma and Mel 202 ocular melanoma cells transduced with the retroviruses DRB1/CD80 express high levels of DRB0101 and CD80 on the cell surface in the absence of Ii.
2546 14996751 Irradiated SUM159PT/DR1/CD80 vaccines stimulate proliferation of non-HLA-DRB0101 peripheral blood mononuclear cells and present an exogenous DR1-restricted tetanus toxoid (TT) peptide, indicating that the transduced DRB0101 is functional.
2547 14996751 SUM159PT/DR1/CD80 vaccines were further transduced with a retrovirus encoding the TT fragment C gene, as a model tumor antigen.
2548 14996751 Depletion and antibody blocking experiments confirm that MHC class II-restricted, endogenously synthesized epitopes are presented to CD4(+) T cells.
2549 14996751 Therefore, the MHC class II vaccines are efficient antigen-presenting cells that activate tumor-specific MHC class II-restricted, CD4(+) T lymphocytes, and they are a novel and potential immunotherapeutic for metastatic cancers.
2550 14996751 We demonstrated previously that the vaccine cells present tumor peptides via the endogenous antigen presentation pathway to activate CD4(+) and CD8(+) T cells.
2551 14996751 To obtain MHC class II(+)CD80(+)Ii(-) human tumor cells, we developed retroviruses encoding HLA-DR and CD80.
2552 14996751 SUM159PT mammary carcinoma and Mel 202 ocular melanoma cells transduced with the retroviruses DRB1/CD80 express high levels of DRB0101 and CD80 on the cell surface in the absence of Ii.
2553 14996751 Irradiated SUM159PT/DR1/CD80 vaccines stimulate proliferation of non-HLA-DRB0101 peripheral blood mononuclear cells and present an exogenous DR1-restricted tetanus toxoid (TT) peptide, indicating that the transduced DRB0101 is functional.
2554 14996751 SUM159PT/DR1/CD80 vaccines were further transduced with a retrovirus encoding the TT fragment C gene, as a model tumor antigen.
2555 14996751 Depletion and antibody blocking experiments confirm that MHC class II-restricted, endogenously synthesized epitopes are presented to CD4(+) T cells.
2556 14996751 Therefore, the MHC class II vaccines are efficient antigen-presenting cells that activate tumor-specific MHC class II-restricted, CD4(+) T lymphocytes, and they are a novel and potential immunotherapeutic for metastatic cancers.
2557 14996751 We demonstrated previously that the vaccine cells present tumor peptides via the endogenous antigen presentation pathway to activate CD4(+) and CD8(+) T cells.
2558 14996751 To obtain MHC class II(+)CD80(+)Ii(-) human tumor cells, we developed retroviruses encoding HLA-DR and CD80.
2559 14996751 SUM159PT mammary carcinoma and Mel 202 ocular melanoma cells transduced with the retroviruses DRB1/CD80 express high levels of DRB0101 and CD80 on the cell surface in the absence of Ii.
2560 14996751 Irradiated SUM159PT/DR1/CD80 vaccines stimulate proliferation of non-HLA-DRB0101 peripheral blood mononuclear cells and present an exogenous DR1-restricted tetanus toxoid (TT) peptide, indicating that the transduced DRB0101 is functional.
2561 14996751 SUM159PT/DR1/CD80 vaccines were further transduced with a retrovirus encoding the TT fragment C gene, as a model tumor antigen.
2562 14996751 Depletion and antibody blocking experiments confirm that MHC class II-restricted, endogenously synthesized epitopes are presented to CD4(+) T cells.
2563 14996751 Therefore, the MHC class II vaccines are efficient antigen-presenting cells that activate tumor-specific MHC class II-restricted, CD4(+) T lymphocytes, and they are a novel and potential immunotherapeutic for metastatic cancers.
2564 14998548 (a) detection of tumour cells in the peripheral blood, bone marrow or lymph node using reverse transcriptase-polymerase chain reaction (RT-PCR)-based measurement of CEA mRNA; (b) targeting of anticancer agents or radionuclides by tumour-selective anti-CEA monoclonal antibodies (mAbs); (c) use of antitumour vaccines capable of eliciting major histocompatibility complex (MHC)-restricted immune responses against CEA-derived peptides.
2565 14998548 Actually, it has been shown that the expression of CEA can be up-regulated by pharmacological agents including, antineoplastic drugs (i.e. 5-fluorouracil), cytokines (i.e. interferons or interleukin-6), differentiating agents (i.e. sodium butyrate) and protein kinase inhibitors (i.e. staurosporine).
2566 14998548 Moreover, the same agents could increase the efficacy of vaccines based on immunogenic CEA-derived peptides restricted by the MHC.
2567 14998548 (a) detection of tumour cells in the peripheral blood, bone marrow or lymph node using reverse transcriptase-polymerase chain reaction (RT-PCR)-based measurement of CEA mRNA; (b) targeting of anticancer agents or radionuclides by tumour-selective anti-CEA monoclonal antibodies (mAbs); (c) use of antitumour vaccines capable of eliciting major histocompatibility complex (MHC)-restricted immune responses against CEA-derived peptides.
2568 14998548 Actually, it has been shown that the expression of CEA can be up-regulated by pharmacological agents including, antineoplastic drugs (i.e. 5-fluorouracil), cytokines (i.e. interferons or interleukin-6), differentiating agents (i.e. sodium butyrate) and protein kinase inhibitors (i.e. staurosporine).
2569 14998548 Moreover, the same agents could increase the efficacy of vaccines based on immunogenic CEA-derived peptides restricted by the MHC.
2570 15000839 The secretion of interferon (IFN)-alpha and IFN-gamma and non-major histocompatability complex (MHC)-restricted cytotoxic activity were assayed with CpG-ODN-stimulated peripheral blood mononuclear cells (PBMC).
2571 15000839 As expected, ODN 2216 was a potent inducer of IFN-alpha secretion by both bovine and ovine PBMC, but ODN 2007 also induced dose-dependent, CpG-specific IFN-alpha secretion by ovine PBMC.
2572 15004163 Nasal Flt3 ligand cDNA elicits CD11c+CD8+ dendritic cells for enhanced mucosal immunity.
2573 15004163 In addition, significant levels of OVA-specific CD4+ T cell proliferative responses and OVA-induced IL-4 and IL-2 production were noted in spleen and cervical lymph nodes.
2574 15004163 Further, marked increases in FL protein occurred in the nasal lamina propria and submandibular glands and the frequencies of CD11c+CD8+ dendritic cells (DCs) significantly increased in the mucosal tissues.
2575 15004163 Moreover, these DCs expressed high levels of CD40, CD80, CD86, and MHC class II molecules.
2576 15009803 The allelic and haplotypic diversity of the HLA-A, HLA-B, and HLA-C loci was investigated in 852 subjects from five sub-Saharan populations from Kenya (Nandi and Luo), Mali (Dogon), Uganda, and Zambia.
2577 15009803 The strength of the LD associations between alleles of HLA-A and HLA-B loci and those of HLA-B and HLA-C loci was on average of the same or higher magnitude as those observed in other non-African populations for the same pairs of loci.
2578 15009803 The allelic and haplotypic diversity of the HLA-A, HLA-B, and HLA-C loci was investigated in 852 subjects from five sub-Saharan populations from Kenya (Nandi and Luo), Mali (Dogon), Uganda, and Zambia.
2579 15009803 The strength of the LD associations between alleles of HLA-A and HLA-B loci and those of HLA-B and HLA-C loci was on average of the same or higher magnitude as those observed in other non-African populations for the same pairs of loci.
2580 15011756 According to the research group of Shortman, experimental results suggest a "dual" DC differentiation model, demonstrating the existence of both myeloid-derived (with characteristic IF: CD11b+, CD11c+, CD8alpha- and DEC205+) and lymphoid-derived DCs (showing CD11b- CD11c-, CD8alpha+ and DEC205+ IF).
2581 15011756 Most of the DCs express immunocytochemically detectable antigens like: S-100, CD1a, CD40 receptor, adhesion molecules (ICAM-1 or CD54, LFA-1 and LFA-3), integrins (CD11a, CD11c and CD18), CD45, CD54, co-stimulatory molecules (B7-1 or CD80, B7-2 or CD86), F418, MHC class I and II and DEC-205, multilectin receptor, immunostimulatory cytokine (IL-12) and, of course, Fc and complement receptors.
2582 15030581 The main proliferating cell types in healthy adult donors were CD16/56(+) and the CD8(+) cells.
2583 15030581 Blocking of major histocompatibility complex (MHC) class II with alpha-MHC class II antibodies markedly inhibited proliferation and interferon-gamma (IFN-gamma) production, whereas interleukin-10 production was not affected.
2584 15030581 Experimental evidence indicates that CD4(+) cells were not necessary for the proliferative and IFN-gamma responses; however, an adherent cell population was required.
2585 15030581 Furthermore, CD16/56(+) cells expressing MHC class II were expanded following P-2 stimulation.
2586 15030581 The main proliferating cell types in healthy adult donors were CD16/56(+) and the CD8(+) cells.
2587 15030581 Blocking of major histocompatibility complex (MHC) class II with alpha-MHC class II antibodies markedly inhibited proliferation and interferon-gamma (IFN-gamma) production, whereas interleukin-10 production was not affected.
2588 15030581 Experimental evidence indicates that CD4(+) cells were not necessary for the proliferative and IFN-gamma responses; however, an adherent cell population was required.
2589 15030581 Furthermore, CD16/56(+) cells expressing MHC class II were expanded following P-2 stimulation.
2590 15031530 In phase I clinical trials of WT1 peptide-based cancer immunotherapy, two patients with advanced lung cancer were intradermally injected with 0.3 mg of an HLA-A*2402-restricted, 9-mer WT1 peptide emulsified with Montanide ISA51 adjuvant.
2591 15034075 Our previous work demonstrated that Trojan Ags containing a CTL epitope localized to intracellular compartments, where MHC class I-binding peptides were generated in a TAP-independent fashion by the action of various exopeptidases and the endopeptidase furin.
2592 15036912 CM were synthesized that had defined lengths and contained aa corresponding to binding motifs of MHC class II molecules relevant in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), specifically HLA-DRB1*1501 and HLA-DRB5*0101, which are related to MS, and H2-IA(s) associated with EAE in SJL mice.
2593 15043207 In recent years, CD4 and CD8 T cell responses to HIV and SIV infection have been increasingly measured with the use of single-cell assays such as ELISPOT, MHC-peptide oligomers, and cytokine flow cytometry.
2594 15043207 These parameters may include functional avidity, epitope breadth and specificity, proliferative capacity, cytokine repertoire, degree of anergy, and differentiation phenotype, as well as magnitude, of HIV-specific CD4 and CD8 T cells.
2595 15046253 CD8 CTL recognize antigenic peptides in the context of class I MHC.
2596 15048588 Moreover, hybrids comprising HLA-A*0201 DCs and allogeneic melanoma tumor cells (Colo 829 cell line) stimulated IFN-gamma secretion by antigen-specific CD8+ T cells, which are restricted for recognition of a melanoma gp100 peptide antigen (gp100(209-217)) within the context of the DC HLA haplotype.
2597 15057902 Further associations were observed with single nucleotide polymorphisms (SNPs) at the IL2 and IL4 loci along with insertion/deletion variants at the IL12B locus (P =.003-.01).
2598 15057902 Host genetic associations were independent of one another as well as other HLA (A, B, C, and DQB1) and cytokine gene (IL4R, IL6, IL10, and TNF) variants.
2599 15068865 Immunization of HLA-A(*)0201-transgenic mice with RT minigenes induced RT-specific cellular responses detected by interferon-gamma secretion.
2600 15069689 Identification of an HLA-A*0201 cytotoxic T lymphocyte epitope specific to the endothelial antigen Tie-2.
2601 15069689 Moreover, CTLs from mice immunised with the modified construct killed HLA-A*0201 endothelial cells overexpressing Tie-2.
2602 15069689 Identification of an HLA-A*0201 cytotoxic T lymphocyte epitope specific to the endothelial antigen Tie-2.
2603 15069689 Moreover, CTLs from mice immunised with the modified construct killed HLA-A*0201 endothelial cells overexpressing Tie-2.
2604 15070762 In contrast, mice with decreased CD4 or MHC class II expression and double-knockout mice deficient in MHC class I- and II-restricted activities were poorly protected or unprotected.
2605 15076142 Phase I trial of antigen-specific gene therapy using a recombinant vaccinia virus encoding MUC-1 and IL-2 in MUC-1-positive patients with advanced prostate cancer.
2606 15076142 The purpose of this phase 1 clinical trial was to determine the maximum tolerated dose, safety of a multiple-dose regimen, and the immunologic effect of vaccinia virus expressing MUC-1 and IL-2 genes (VV/MUC-1/IL-2) in patients with advanced prostate cancer.
2607 15076142 Systemic immune modulation in this patient included (1) up-regulation of IL-2 (CD25) and T cell (TcR alphabeta) receptors, (2) increase in the CD4/CD8 ratio (2.5-fold) (3) augmentation of T-helper type 1 cell (TH1) (interferon-gamma and tumor necrosis factor-alpha) but not TH2 (IL-4) cytokine mRNA expression, (4) induction of natural killer cell activity and MHC independent MUC-1 specific cytotoxic T-cell activity, and (5) normalization of mRNA expression of T-cell-associated signal transduction molecules TcR-zeta and p56lck.
2608 15076142 These results suggest that VV/MUC-1/IL-2 gene therapy with a maximum tolerated dose of 5 x 10(7) pfu is safe and well tolerated.
2609 15087407 Three IEX-1-derived peptides at positions 47-56, 61-69, and 65-73, which were recognized by the 850B-CTLs, could induce CD8(+) peptide-specific CTL reaction to tumor cells from HLA-A33(+) gastric cancer patients and other epithelial cancer patients, but not from healthy donors, in an HLA class I-restricted manner.
2610 15094217 The development of folate/antibody conjugates specific for the T cell co-stimulatory molecule CD28 could yield activated T cells that recognize endogenous peptide-major histocompatibility complex (MHC) antigens on tumor cells.
2611 15094367 After intravenous administration, OVA mRNA expression and MHC class I-restricted antigen presentation on CD11c+ cells and inflammatory cytokines, such as TNF-alpha, IL-12, and IFN-gamma, that can enhance the Th1 response of the Man liposome/pCMV-OVA complex were higher than that of naked pCMV-OVA and that complexed with DC-Chol liposomes.
2612 15102666 Generation of carcinoembryonic antigen (CEA)-specific T-cell responses in HLA-A*0201 and HLA-A*2402 late-stage colorectal cancer patients after vaccination with dendritic cells loaded with CEA peptides.
2613 15122754 HCs upregulate surface expression of major histocompatibility complex (MHC) class I molecules and CD1d but not MHC class II molecules Qa-1, CD80, CD86, CD54, or CD95; in addition, they expressed/secreted interleukin (IL)-10 and IL-4 but not IL-1, IL-6, IL-13, interferon (IFN)-gamma, tumor necrosis factor (TNF), IL-4, or IL-27 (i.e., they acquire the HC* phenotype).
2614 15122754 HCs* (but not HCs) induced specific activation, proliferation, and IFN-gamma, TNF, and IL-13 release of cocultured naïve CD8(+) T cells.
2615 15122754 Only recently activated CD8(+) T blasts (but not recently activated CD4(+) T blasts or activated cells of the innate immune system, including natural killer T [NKT] cells) induced the HC* phenotype that is prominent from day 10 to day 20 postvaccination (i.e., time points at which peak numbers of recently primed CD8(+) T blasts are found in the liver).
2616 15128786 Both vectors induced IL-12 and TNF-alpha, but only Lm-LLO-E7 induced IL-2 production by DCs.
2617 15128786 Lm-LLO-E7 also induced significantly higher levels of MHC class II molecules, CD40, and B7 costimulatory molecules (CD86, B7-H1, and B7-DC) on DCs than Lm-E7.
2618 15128786 A similar shift is also observed for B7-H1 and B7-DC molecules.
2619 15128805 In view of this apparent association of HLA-A*1101 with resistance to acquisition of HIV-1 infection, and given the importance of eliciting strong CTL responses to control and eliminate HIV-1, we have determined the crystal structure of HLA-A*1101 complexed with two immunodominant HIV-1 CTL epitopes: the nonamer reverse transcriptase(313-321) (AIFQSSMTK) and decamer Nef(73-82) (QVPLRPMTYK) peptides.
2620 15129672 Antigen presentation by major histocompatibility complex type II (MHC II) molecules and activation of CD4+ helper T cells are critical for the generation of immunological memory.
2621 15129672 The LAMP/gag chimera protein traffics to the MHC II compartment of transfected cells and elicits enhanced immune responses as compared to a DNA vaccine encoding native gag not targeted to the MHC II compartment.
2622 15129672 We have now investigated the long-term responses of immunized mice and show that the LAMP/gag DNA vaccine promotes long-lasting B cell- and CD4+ and CD8+ T-cell memory responses induced by DNA encoding non-targeted Gag decay rapidly and elicit very low or undetectable levels of gag DNA is sufficient to generate T-cell memory.
2623 15129672 Following this initial priming immunization with LAMP/gag DNA, booster immunizations with native gag DNA or the LAMP/gag chimera are equally efficient in eliciting B- and T-cell secondary responses, results in accordance with observations that secondary expansion of CD8+ cells in the boost phase does not require additional CD4+ help.
2624 15129672 Antigen presentation by major histocompatibility complex type II (MHC II) molecules and activation of CD4+ helper T cells are critical for the generation of immunological memory.
2625 15129672 The LAMP/gag chimera protein traffics to the MHC II compartment of transfected cells and elicits enhanced immune responses as compared to a DNA vaccine encoding native gag not targeted to the MHC II compartment.
2626 15129672 We have now investigated the long-term responses of immunized mice and show that the LAMP/gag DNA vaccine promotes long-lasting B cell- and CD4+ and CD8+ T-cell memory responses induced by DNA encoding non-targeted Gag decay rapidly and elicit very low or undetectable levels of gag DNA is sufficient to generate T-cell memory.
2627 15129672 Following this initial priming immunization with LAMP/gag DNA, booster immunizations with native gag DNA or the LAMP/gag chimera are equally efficient in eliciting B- and T-cell secondary responses, results in accordance with observations that secondary expansion of CD8+ cells in the boost phase does not require additional CD4+ help.
2628 15140052 These fusion cells expressed major histocompatibility complexes (MHC) class I and II, CD86, CD11c and CD8alpha.
2629 15140052 Splenocytes from mice vaccinated with fusion cells showed increased production of interferon-gamma (IFN-gamma) and cytotoxic T-lymphocyte (CTL) activity as compared with those vaccinated with DCs or tumour cells alone, and CTL levels were higher in fusion/IL-2-vaccinated mice than in fusion/LacZ-vaccinated mice.
2630 15153480 Messenger RNA-electroporated dendritic cells presenting MAGE-A3 simultaneously in HLA class I and class II molecules.
2631 15153480 An optimal anticancer vaccine probably requires the cooperation of both CD4(+) Th cells and CD8(+) CTLs.
2632 15153480 In this study we compared the efficiency of the targeting signals of invariant chain, lysosome-associated membrane protein-1 (LAMP1) and DC-LAMP.
2633 15153480 DCs were also electroporated with unmodified MAGE-A3 or MAGE-A3 linked to the targeting signals, and the presentation of MAGE-A3-derived epitopes in the context of HLA class I and class II molecules was investigated.
2634 15153480 Proteins linked to the LAMP1 or DC-LAMP signal are more efficiently presented than proteins linked to the invariant chain-targeting signal.
2635 15153480 Messenger RNA-electroporated dendritic cells presenting MAGE-A3 simultaneously in HLA class I and class II molecules.
2636 15153480 An optimal anticancer vaccine probably requires the cooperation of both CD4(+) Th cells and CD8(+) CTLs.
2637 15153480 In this study we compared the efficiency of the targeting signals of invariant chain, lysosome-associated membrane protein-1 (LAMP1) and DC-LAMP.
2638 15153480 DCs were also electroporated with unmodified MAGE-A3 or MAGE-A3 linked to the targeting signals, and the presentation of MAGE-A3-derived epitopes in the context of HLA class I and class II molecules was investigated.
2639 15153480 Proteins linked to the LAMP1 or DC-LAMP signal are more efficiently presented than proteins linked to the invariant chain-targeting signal.
2640 15153482 CD8 T lymphocytes (CTL) responsive to immunodominant minor histocompatibility (minor H) Ags are thought to play a disproportionate role in allograft rejection in MHC-identical solid and bone marrow transplant settings.
2641 15160996 In this study, we investigated the specific CTL-inducing activity of 5 HLA-A*2402-restricted peptides derived from gp100, tyrosinase, MAGE1, MAGE2 and MAGE3.
2642 15164233 Peptide extracts derived from primary HLA-A*0201-positive (+) HER-2/neu+ human tumors by acid elution (acid cell extracts (ACEs)) were tested for their capacity to elicit in HLA-A*0201 transgenic mice, cytotoxic T lymphocytes (CTLs) lysing HLA-A*0201+ HER-2/neu+ tumor cells.
2643 15164233 Injections of ACE in transgenic mice induced CTLs capable of specifically lysing HER-2/neu+ tumor cell lines (also including the original HER-2/neu+ primary tumor cells from which the ACEs were derived) in an HLA-A*0201-restricted fashion.
2644 15164233 Adoptive transfer of ACE-induced CTLs was sufficient to significantly prolong survival of SCID mice inoculated with HLA-A*0201+ HER-2/ neu+ human tumor cell lines.
2645 15164233 Cytotoxicity of such ACE-induced CTL lines was directed, at least as detected herein, also against the HER-2/ neu peptides HER-2 (9(369)) and HER-2 (9(435)) demonstrating the immunodominance of these epitopes.
2646 15164233 HER-2 peptide-specific CTLs generated in the HLA-A*0201-transgenic mice, upon peptide immunization, lysed in vitro HER-2/neu+ human tumor cell lines in an HLA-A*0201-restricted manner and, when adoptively transferred, conferred sufficient protection in SCID mice inoculated with the same human tumor cell lines as above.
2647 15164233 However, CTLs induced by ACEs displayed enhanced efficacy in the therapy of xenografted SCID mice compared with the HER-2 peptide-specific CTLs (i.e., HER-2 [9(369)] or HER-2 [9(435)]).
2648 15164233 Thus, immunization with ACEs from HER-2/neu+ primary tumor cells appears to be an effective approach to generate multiple and potent CTL-mediated immune responses against HER-2/neu+ tumors expressing the appropriate HLA allele(s).
2649 15164233 By screening ACE-induced CTL lines with synthetic peptides encompassing the HER-2/neu sequence, it is feasible to identify immunodominant epitopes which may be used in mixtures as vaccines with enhanced efficacy in both the prevention and therapy of HER-2/neu+ malignancies.
2650 15164233 Peptide extracts derived from primary HLA-A*0201-positive (+) HER-2/neu+ human tumors by acid elution (acid cell extracts (ACEs)) were tested for their capacity to elicit in HLA-A*0201 transgenic mice, cytotoxic T lymphocytes (CTLs) lysing HLA-A*0201+ HER-2/neu+ tumor cells.
2651 15164233 Injections of ACE in transgenic mice induced CTLs capable of specifically lysing HER-2/neu+ tumor cell lines (also including the original HER-2/neu+ primary tumor cells from which the ACEs were derived) in an HLA-A*0201-restricted fashion.
2652 15164233 Adoptive transfer of ACE-induced CTLs was sufficient to significantly prolong survival of SCID mice inoculated with HLA-A*0201+ HER-2/ neu+ human tumor cell lines.
2653 15164233 Cytotoxicity of such ACE-induced CTL lines was directed, at least as detected herein, also against the HER-2/ neu peptides HER-2 (9(369)) and HER-2 (9(435)) demonstrating the immunodominance of these epitopes.
2654 15164233 HER-2 peptide-specific CTLs generated in the HLA-A*0201-transgenic mice, upon peptide immunization, lysed in vitro HER-2/neu+ human tumor cell lines in an HLA-A*0201-restricted manner and, when adoptively transferred, conferred sufficient protection in SCID mice inoculated with the same human tumor cell lines as above.
2655 15164233 However, CTLs induced by ACEs displayed enhanced efficacy in the therapy of xenografted SCID mice compared with the HER-2 peptide-specific CTLs (i.e., HER-2 [9(369)] or HER-2 [9(435)]).
2656 15164233 Thus, immunization with ACEs from HER-2/neu+ primary tumor cells appears to be an effective approach to generate multiple and potent CTL-mediated immune responses against HER-2/neu+ tumors expressing the appropriate HLA allele(s).
2657 15164233 By screening ACE-induced CTL lines with synthetic peptides encompassing the HER-2/neu sequence, it is feasible to identify immunodominant epitopes which may be used in mixtures as vaccines with enhanced efficacy in both the prevention and therapy of HER-2/neu+ malignancies.
2658 15164233 Peptide extracts derived from primary HLA-A*0201-positive (+) HER-2/neu+ human tumors by acid elution (acid cell extracts (ACEs)) were tested for their capacity to elicit in HLA-A*0201 transgenic mice, cytotoxic T lymphocytes (CTLs) lysing HLA-A*0201+ HER-2/neu+ tumor cells.
2659 15164233 Injections of ACE in transgenic mice induced CTLs capable of specifically lysing HER-2/neu+ tumor cell lines (also including the original HER-2/neu+ primary tumor cells from which the ACEs were derived) in an HLA-A*0201-restricted fashion.
2660 15164233 Adoptive transfer of ACE-induced CTLs was sufficient to significantly prolong survival of SCID mice inoculated with HLA-A*0201+ HER-2/ neu+ human tumor cell lines.
2661 15164233 Cytotoxicity of such ACE-induced CTL lines was directed, at least as detected herein, also against the HER-2/ neu peptides HER-2 (9(369)) and HER-2 (9(435)) demonstrating the immunodominance of these epitopes.
2662 15164233 HER-2 peptide-specific CTLs generated in the HLA-A*0201-transgenic mice, upon peptide immunization, lysed in vitro HER-2/neu+ human tumor cell lines in an HLA-A*0201-restricted manner and, when adoptively transferred, conferred sufficient protection in SCID mice inoculated with the same human tumor cell lines as above.
2663 15164233 However, CTLs induced by ACEs displayed enhanced efficacy in the therapy of xenografted SCID mice compared with the HER-2 peptide-specific CTLs (i.e., HER-2 [9(369)] or HER-2 [9(435)]).
2664 15164233 Thus, immunization with ACEs from HER-2/neu+ primary tumor cells appears to be an effective approach to generate multiple and potent CTL-mediated immune responses against HER-2/neu+ tumors expressing the appropriate HLA allele(s).
2665 15164233 By screening ACE-induced CTL lines with synthetic peptides encompassing the HER-2/neu sequence, it is feasible to identify immunodominant epitopes which may be used in mixtures as vaccines with enhanced efficacy in both the prevention and therapy of HER-2/neu+ malignancies.
2666 15164233 Peptide extracts derived from primary HLA-A*0201-positive (+) HER-2/neu+ human tumors by acid elution (acid cell extracts (ACEs)) were tested for their capacity to elicit in HLA-A*0201 transgenic mice, cytotoxic T lymphocytes (CTLs) lysing HLA-A*0201+ HER-2/neu+ tumor cells.
2667 15164233 Injections of ACE in transgenic mice induced CTLs capable of specifically lysing HER-2/neu+ tumor cell lines (also including the original HER-2/neu+ primary tumor cells from which the ACEs were derived) in an HLA-A*0201-restricted fashion.
2668 15164233 Adoptive transfer of ACE-induced CTLs was sufficient to significantly prolong survival of SCID mice inoculated with HLA-A*0201+ HER-2/ neu+ human tumor cell lines.
2669 15164233 Cytotoxicity of such ACE-induced CTL lines was directed, at least as detected herein, also against the HER-2/ neu peptides HER-2 (9(369)) and HER-2 (9(435)) demonstrating the immunodominance of these epitopes.
2670 15164233 HER-2 peptide-specific CTLs generated in the HLA-A*0201-transgenic mice, upon peptide immunization, lysed in vitro HER-2/neu+ human tumor cell lines in an HLA-A*0201-restricted manner and, when adoptively transferred, conferred sufficient protection in SCID mice inoculated with the same human tumor cell lines as above.
2671 15164233 However, CTLs induced by ACEs displayed enhanced efficacy in the therapy of xenografted SCID mice compared with the HER-2 peptide-specific CTLs (i.e., HER-2 [9(369)] or HER-2 [9(435)]).
2672 15164233 Thus, immunization with ACEs from HER-2/neu+ primary tumor cells appears to be an effective approach to generate multiple and potent CTL-mediated immune responses against HER-2/neu+ tumors expressing the appropriate HLA allele(s).
2673 15164233 By screening ACE-induced CTL lines with synthetic peptides encompassing the HER-2/neu sequence, it is feasible to identify immunodominant epitopes which may be used in mixtures as vaccines with enhanced efficacy in both the prevention and therapy of HER-2/neu+ malignancies.
2674 15165177 HLA class I and class II, TAP, and HLA-DM allele associations with measles-specific antibody levels following measles vaccination have revealed, in part, the immunologic basis for mechanisms of measles immunity variation.
2675 15172451 MHC class II tetramers containing influenza hemagglutinin and EBV EBNA1 epitopes detect reliably specific CD4(+) T cells in healthy volunteers.
2676 15172451 Progress has been made primarily using MHC class I tetramers to monitor CD8(+) T cells, whereas corresponding efforts to stain CD4(+) T cells with class II tetramers have not been as successful.
2677 15172451 The frequency of antigen-specific CD4(+) T cells is lower than the frequency of CD8(+) T cells and (2). some, but not all, antigen- specific CD4(+) T cells can bind tetramer because of low functional avidity.
2678 15172451 The data indicate that MHC class II tetramers can be used reliably for the identification of CD4(+) T cells specific for ubiquitous infectious agents in normal donors.
2679 15172451 MHC class II tetramers containing influenza hemagglutinin and EBV EBNA1 epitopes detect reliably specific CD4(+) T cells in healthy volunteers.
2680 15172451 Progress has been made primarily using MHC class I tetramers to monitor CD8(+) T cells, whereas corresponding efforts to stain CD4(+) T cells with class II tetramers have not been as successful.
2681 15172451 The frequency of antigen-specific CD4(+) T cells is lower than the frequency of CD8(+) T cells and (2). some, but not all, antigen- specific CD4(+) T cells can bind tetramer because of low functional avidity.
2682 15172451 The data indicate that MHC class II tetramers can be used reliably for the identification of CD4(+) T cells specific for ubiquitous infectious agents in normal donors.
2683 15172451 MHC class II tetramers containing influenza hemagglutinin and EBV EBNA1 epitopes detect reliably specific CD4(+) T cells in healthy volunteers.
2684 15172451 Progress has been made primarily using MHC class I tetramers to monitor CD8(+) T cells, whereas corresponding efforts to stain CD4(+) T cells with class II tetramers have not been as successful.
2685 15172451 The frequency of antigen-specific CD4(+) T cells is lower than the frequency of CD8(+) T cells and (2). some, but not all, antigen- specific CD4(+) T cells can bind tetramer because of low functional avidity.
2686 15172451 The data indicate that MHC class II tetramers can be used reliably for the identification of CD4(+) T cells specific for ubiquitous infectious agents in normal donors.
2687 15173207 Expansion of melanoma-specific cytolytic CD8+ T cell precursors in patients with metastatic melanoma vaccinated with CD34+ progenitor-derived dendritic cells.
2688 15173207 We have shown earlier, in 18 human histocompatibility leukocyte antigen (HLA)-A*0201 patients with metastatic melanoma, that vaccination with peptide-loaded CD34-dendritic cells (DCs) leads to expansion of melanoma-specific interferon gamma-producing CD8+ T cells in the blood.
2689 15181279 We performed Cr51 cytotoxic T lymphocyte (CTL), interferon-gamma (IFN-gamma) ELISPOT, and proliferation assays as well as genetic studies, including HLA-class I typing.
2690 15186397 As a result of this intracellular lifestyle, the pathways for the induction of MHC I- and CD1-restricted CD8 T cells by such microorganisms remain elusive.
2691 15191787 The ISCOM efficiently evokes CD8+, MHC class 1 restricted T cell response.
2692 15193402 PLGA nanoparticles were efficiently phagocytosed by the DCs (CD11c+, MHC class II+, CD86+) in culture, resulting in their intracellular localization.
2693 15207780 Vaccination with OVA-CT-pulsed DC concurrently induced strong CTL in vitro activity and anti-E.G7 tumor protection in vivo in WT, NK-depleted and CD4-deficient mice as well as in IL-12-/- and IFN-gamma-/- mice but not in CD8-deficient mice.
2694 15207780 Importantly, activation of CTL by OVA-CT-pulsed DC was dependent on CT-induced activation of adenylate cyclase and increased cAMP production by DC associated with increased expression of MHC class I and co-stimulatory molecules (CD80, CD86 and CD40).
2695 15214037 A naked Sindbis RNA replicon vector (SINrep5) encoding the herpes simplex virus type 1 protein VP22 linked to E7 (SINrep5-VP22/E7) generated significant antitumor effects against TC-1 and TC-1 P3(A15), tumors with down-regulated MHC class I expression.
2696 15234529 These elements encode molecules that present self and non-self peptide fragments to both CD4+ and CD8+ cytolytic T lymphocytes (CTL).
2697 15234529 HSPs, in particular glucose-regulated peptide 94 (GRP94), HSP70 and to a lesser extent HSP90, bind peptides that are immunogenic in vitro and in vivo.
2698 15234529 Whether a separate genetic program evolved in addition to MHC that increases the antigenic repertoire of the cell or if this newly observed function of HSP is predominantly a laboratory-based phenomena and/or a normal chaperone function of this family of proteins remains to be answered.
2699 15254748 They can be repaired, at least partially and in vitro, by cytokines (IFNgamma, TNFalpha) or by DNA demethylation/histone hyperacetylation procedures.
2700 15254748 The innate and adaptive antitumour immunity may be under some conditions interconnected: primary activation of the MHC class I-unrestricted surveillance mechanisms may lead to the production of IFNgamma by the activated NK/gammadelta T cells; the in situ produced IFNgamma may then up-regulate the MHC class I molecule expression on the tumour cell surface and in this way it may stimulate the more efficient, MHC class I-restricted, adaptive immunity.
2701 15254748 Either therapeutic procedures aiming at up-regulation of MHC class I expression, or enhancement of MHC class I-unrestricted (CD4+, NK, NKT, gammadelta T) tumour defence effector mechanisms by dendritic cell-based therapeutic vaccines, by cytokines (IL-2, IL-12, IFNgamma, GM-CSF), or by the cytokine gene-based, genetically modified tumour vaccines should be considered.
2702 15254748 They can be repaired, at least partially and in vitro, by cytokines (IFNgamma, TNFalpha) or by DNA demethylation/histone hyperacetylation procedures.
2703 15254748 The innate and adaptive antitumour immunity may be under some conditions interconnected: primary activation of the MHC class I-unrestricted surveillance mechanisms may lead to the production of IFNgamma by the activated NK/gammadelta T cells; the in situ produced IFNgamma may then up-regulate the MHC class I molecule expression on the tumour cell surface and in this way it may stimulate the more efficient, MHC class I-restricted, adaptive immunity.
2704 15254748 Either therapeutic procedures aiming at up-regulation of MHC class I expression, or enhancement of MHC class I-unrestricted (CD4+, NK, NKT, gammadelta T) tumour defence effector mechanisms by dendritic cell-based therapeutic vaccines, by cytokines (IL-2, IL-12, IFNgamma, GM-CSF), or by the cytokine gene-based, genetically modified tumour vaccines should be considered.
2705 15259007 Removal of the stratum corneum increased expression of MHC class II, CD86, CD40, CD54 and CD11c on Langerhans cells, but did not cause them to migrate.
2706 15265933 Strong CD4(+) and CD8(+) T cell responses are considered important immune components for controlling HIV infection, and their priming may be central to an effective HIV vaccine.
2707 15265933 We describe in this study an approach by which multiple CD4(+) and CD8(+) T cell epitopes are processed and presented from an exogenously added HIV-1 Gag-p24 peptide of 32 aa complexed to heat shock protein (HSP) gp96.
2708 15265933 CD8(+) T cell recognition of the HSP/peptide complex, but not the peptide alone, was inhibited by brefeldin A, suggesting an endoplasmic reticulum-dependent pathway.
2709 15265933 Given previous reports of the strong immunogenicity of HSP/peptide complexes, the present data suggest that HSP-complexed peptides containing multiple MHC class I- and class II-restricted epitopes represent potential vaccine candidates for HIV and other viral infections suitable to induce effective CTL memory by simultaneously providing CD4 T cell help.
2710 15265949 The presence of anti-SL9 responses was determined using a panel of highly sensitive cellular immunoassays, including peptide:MHC tetramer binding, IFN-gamma ELISPOT, and cytokine flow cytometry.
2711 15265949 Thirteen HLA-A*0201 vaccinees with documented anti-Gag CD8 CTL reactivities were tested, and none had a detectable anti-SL9 response.
2712 15265949 The presence of anti-SL9 responses was determined using a panel of highly sensitive cellular immunoassays, including peptide:MHC tetramer binding, IFN-gamma ELISPOT, and cytokine flow cytometry.
2713 15265949 Thirteen HLA-A*0201 vaccinees with documented anti-Gag CD8 CTL reactivities were tested, and none had a detectable anti-SL9 response.
2714 15294974 We report the use of a novel pH-triggered microparticle that exploits the ability of APCs to cross-present MHC I-restricted Ags that have been engulfed in the low pH environment of the phagosome.
2715 15294974 Encapsulation of MHC I epitopes in pH-triggered microparticles increases Ag presentation and may improve CD8(+) T cell priming to peptide vaccines against viruses and cancer.
2716 15294974 We report the use of a novel pH-triggered microparticle that exploits the ability of APCs to cross-present MHC I-restricted Ags that have been engulfed in the low pH environment of the phagosome.
2717 15294974 Encapsulation of MHC I epitopes in pH-triggered microparticles increases Ag presentation and may improve CD8(+) T cell priming to peptide vaccines against viruses and cancer.
2718 15297401 In this pilot study, we show that immunization of three resected, high-risk metastatic melanoma patients with a T-helper epitope derived from the melanoma differentiation antigen, melanoma antigen recognized by T cells-1, results in CD4(+) T-cell immune responses.
2719 15297401 Immune reactivity to that epitope was detected by DR4-peptide tetramer staining, and enzyme-linked immunospot assay of fresh and restimulated CD4(+) T cells from patients over the course of the 12-month vaccine regimen.
2720 15297401 For 1 DRbeta1*0401(+) patient, antigen-specific CD4(+) T cells recognized human leukocyte antigen-matched antigen-expressing tumor cells, secreted granzyme B, and also exhibited cytolysis that was MHC class II-restricted.
2721 15298487 HLA class I expression in cell lines was enhanced upon treatment with IFN-gamma.
2722 15298487 Interestingly, a spontaneous humoral and CD8+ T cellular response to the CTA NY-ESO-1 was detected in a synovial sarcoma patient.
2723 15304005 HLA class I serotypes and cytotoxic T-lymphocyte responses among human immunodeficiency virus-1-uninfected Thai volunteers immunized with ALVAC-HIV in combination with monomeric gp120 or oligomeric gp160 protein boosting.
2724 15304005 In the setting of two, phase I/II human immunodeficiency virus-1 vaccine trials of a recombinant canarypox prime, and boosting with either recombinant monomeric gp120 or oligomeric gp160, we assessed the association between specific human leukocyte antigen (HLA) class I serotypes and the presence of cytotoxic T-lymphocyte response measured by 51Cr-release assay.
2725 15304005 HLA class I serotypes A11, A24, A33, B46, and B75 were the most common, present in 10% or more of 245 individuals studied.
2726 15304005 Forty of 187 (21.4%) Thai adults who received either ALVAC-HIV with gp120 or oligomeric gp160 or ALVAC alone had a precursor cytolytic CD8 T-cell response (pCTL).
2727 15304005 HLA class I serotypes and cytotoxic T-lymphocyte responses among human immunodeficiency virus-1-uninfected Thai volunteers immunized with ALVAC-HIV in combination with monomeric gp120 or oligomeric gp160 protein boosting.
2728 15304005 In the setting of two, phase I/II human immunodeficiency virus-1 vaccine trials of a recombinant canarypox prime, and boosting with either recombinant monomeric gp120 or oligomeric gp160, we assessed the association between specific human leukocyte antigen (HLA) class I serotypes and the presence of cytotoxic T-lymphocyte response measured by 51Cr-release assay.
2729 15304005 HLA class I serotypes A11, A24, A33, B46, and B75 were the most common, present in 10% or more of 245 individuals studied.
2730 15304005 Forty of 187 (21.4%) Thai adults who received either ALVAC-HIV with gp120 or oligomeric gp160 or ALVAC alone had a precursor cytolytic CD8 T-cell response (pCTL).
2731 15304005 HLA class I serotypes and cytotoxic T-lymphocyte responses among human immunodeficiency virus-1-uninfected Thai volunteers immunized with ALVAC-HIV in combination with monomeric gp120 or oligomeric gp160 protein boosting.
2732 15304005 In the setting of two, phase I/II human immunodeficiency virus-1 vaccine trials of a recombinant canarypox prime, and boosting with either recombinant monomeric gp120 or oligomeric gp160, we assessed the association between specific human leukocyte antigen (HLA) class I serotypes and the presence of cytotoxic T-lymphocyte response measured by 51Cr-release assay.
2733 15304005 HLA class I serotypes A11, A24, A33, B46, and B75 were the most common, present in 10% or more of 245 individuals studied.
2734 15304005 Forty of 187 (21.4%) Thai adults who received either ALVAC-HIV with gp120 or oligomeric gp160 or ALVAC alone had a precursor cytolytic CD8 T-cell response (pCTL).
2735 15314544 In an open-label phase 2 trial, 10(7) autologous ex vivo generated DCs pulsed with the HLA-A*0201 immunodominant peptide MART-1(27-35) were administered to 10 subjects with stage II-IV melanoma.
2736 15314544 Of four patients with measurable disease, one had stable disease for 6 months and another has a continued complete response for over 2 years, which is confounded by receiving a closely sequenced CTLA4 blocking antibody.
2737 15314544 The DC vaccines induced determinant spreading in this subject, and CTLA4 blockade reactivated T cells with prior antigen exposure.
2738 15314544 Sequential CTLA4 blockade may enhance the immune activity of DC-based immunotherapy.
2739 15361243 These organisms, which normally reside in a late endosomal, major histocompatibility complex (MHC) class II(+) compartment within host macrophages cells, require CD4(+) T-cell responses for the control of disease.
2740 15365188 Patients were intradermally injected with an HLA-A*2402-restricted, natural, or modified 9-mer WT1 peptide emulsified with Montanide ISA51 adjuvant at 0.3, 1.0, or 3.0 mg per body at 2-week intervals, with toxicity and clinical and immunological responses as the principal endpoints.
2741 15365776 A CD80-transfected human breast cancer cell variant induces HER-2/neu-specific T cells in HLA-A*02-matched situations in vitro as well as in vivo.
2742 15365776 Using CD80+ KS breast cancer cells and human leukocyte antigen (HLA)-A*02-matched peripheral blood mononuclear cells (PBMCs) of breast cancer patients in allogeneic mixed lymphocyte-tumor cell cultures (MLTCs), it was possible to isolate HLA-A*02-restricted cytotoxic T cells (CTLs).
2743 15365776 KS breast cancer cells were demonstrated to express already known TAAs such as CEA, MUC-1, MAGE-1, MAGE-2, and MAGE-3.
2744 15365776 To further improve antigenicity, HER-2/neu was added to this panel as a marker antigen known to elicit HLA-A*02-restricted CTLs in patients with breast cancer.
2745 15365776 Thus, the antigen-processing and antigen-presentation capacity of KS cells was further demonstrated by the stimulation of HER-2/neu-specific CD8+ T cells in PBMCs of breast cancer patients in vitro.
2746 15365776 These results gave a good rationale for a phase I/II trial, where the CD80+ HER-2/neu-overexpressing KS variant is actually used as a cellular vaccine in patients with metastatic breast cancer.
2747 15365776 As a proof of principle, we present data from two patients where a significant increase of interferon-gamma (IFN-gamma) release was detected when postvaccination PBMCs were stimulated by allogeneic vaccine cells as well as by HLA-A*02-restricted HER-2/neu epitopes.
2748 15365776 A CD80-transfected human breast cancer cell variant induces HER-2/neu-specific T cells in HLA-A*02-matched situations in vitro as well as in vivo.
2749 15365776 Using CD80+ KS breast cancer cells and human leukocyte antigen (HLA)-A*02-matched peripheral blood mononuclear cells (PBMCs) of breast cancer patients in allogeneic mixed lymphocyte-tumor cell cultures (MLTCs), it was possible to isolate HLA-A*02-restricted cytotoxic T cells (CTLs).
2750 15365776 KS breast cancer cells were demonstrated to express already known TAAs such as CEA, MUC-1, MAGE-1, MAGE-2, and MAGE-3.
2751 15365776 To further improve antigenicity, HER-2/neu was added to this panel as a marker antigen known to elicit HLA-A*02-restricted CTLs in patients with breast cancer.
2752 15365776 Thus, the antigen-processing and antigen-presentation capacity of KS cells was further demonstrated by the stimulation of HER-2/neu-specific CD8+ T cells in PBMCs of breast cancer patients in vitro.
2753 15365776 These results gave a good rationale for a phase I/II trial, where the CD80+ HER-2/neu-overexpressing KS variant is actually used as a cellular vaccine in patients with metastatic breast cancer.
2754 15365776 As a proof of principle, we present data from two patients where a significant increase of interferon-gamma (IFN-gamma) release was detected when postvaccination PBMCs were stimulated by allogeneic vaccine cells as well as by HLA-A*02-restricted HER-2/neu epitopes.
2755 15365776 A CD80-transfected human breast cancer cell variant induces HER-2/neu-specific T cells in HLA-A*02-matched situations in vitro as well as in vivo.
2756 15365776 Using CD80+ KS breast cancer cells and human leukocyte antigen (HLA)-A*02-matched peripheral blood mononuclear cells (PBMCs) of breast cancer patients in allogeneic mixed lymphocyte-tumor cell cultures (MLTCs), it was possible to isolate HLA-A*02-restricted cytotoxic T cells (CTLs).
2757 15365776 KS breast cancer cells were demonstrated to express already known TAAs such as CEA, MUC-1, MAGE-1, MAGE-2, and MAGE-3.
2758 15365776 To further improve antigenicity, HER-2/neu was added to this panel as a marker antigen known to elicit HLA-A*02-restricted CTLs in patients with breast cancer.
2759 15365776 Thus, the antigen-processing and antigen-presentation capacity of KS cells was further demonstrated by the stimulation of HER-2/neu-specific CD8+ T cells in PBMCs of breast cancer patients in vitro.
2760 15365776 These results gave a good rationale for a phase I/II trial, where the CD80+ HER-2/neu-overexpressing KS variant is actually used as a cellular vaccine in patients with metastatic breast cancer.
2761 15365776 As a proof of principle, we present data from two patients where a significant increase of interferon-gamma (IFN-gamma) release was detected when postvaccination PBMCs were stimulated by allogeneic vaccine cells as well as by HLA-A*02-restricted HER-2/neu epitopes.
2762 15365776 A CD80-transfected human breast cancer cell variant induces HER-2/neu-specific T cells in HLA-A*02-matched situations in vitro as well as in vivo.
2763 15365776 Using CD80+ KS breast cancer cells and human leukocyte antigen (HLA)-A*02-matched peripheral blood mononuclear cells (PBMCs) of breast cancer patients in allogeneic mixed lymphocyte-tumor cell cultures (MLTCs), it was possible to isolate HLA-A*02-restricted cytotoxic T cells (CTLs).
2764 15365776 KS breast cancer cells were demonstrated to express already known TAAs such as CEA, MUC-1, MAGE-1, MAGE-2, and MAGE-3.
2765 15365776 To further improve antigenicity, HER-2/neu was added to this panel as a marker antigen known to elicit HLA-A*02-restricted CTLs in patients with breast cancer.
2766 15365776 Thus, the antigen-processing and antigen-presentation capacity of KS cells was further demonstrated by the stimulation of HER-2/neu-specific CD8+ T cells in PBMCs of breast cancer patients in vitro.
2767 15365776 These results gave a good rationale for a phase I/II trial, where the CD80+ HER-2/neu-overexpressing KS variant is actually used as a cellular vaccine in patients with metastatic breast cancer.
2768 15365776 As a proof of principle, we present data from two patients where a significant increase of interferon-gamma (IFN-gamma) release was detected when postvaccination PBMCs were stimulated by allogeneic vaccine cells as well as by HLA-A*02-restricted HER-2/neu epitopes.
2769 15368308 Dissecting cytotoxic T cell responses towards the NY-ESO-1 protein by peptide/MHC-specific antibody fragments.
2770 15368308 A detailed analysis of CD8(+) T cells generated in vaccine trials using NY-ESO-1-derived peptides (157-165 and 157-167) revealed that the dominant immune response was directed against a cryptic epitope (159-167) diverting the immune response from tumor recognition.
2771 15368308 The antibody fragment blocked in a dose-dependent fashion the recognition of NY-ESO-1/HLA-A2-positive tumor cells by NY-ESO-1(157-165) peptide-specific CD8(+) T cells.
2772 15378283 We have developed a mass spectrometric approach which can be used to determine if an antigenic peptide is naturally processed and presented by any given MHC class I molecule.
2773 15378283 The use of this technology negates the need to test peptides for their ability to stimulate CTL responses in those cases where the peptide is not naturally processed and bound to the target MHC class I molecule of interest, thus allowing resources to be focused on the most promising vaccine candidates.
2774 15378283 We have developed a mass spectrometric approach which can be used to determine if an antigenic peptide is naturally processed and presented by any given MHC class I molecule.
2775 15378283 The use of this technology negates the need to test peptides for their ability to stimulate CTL responses in those cases where the peptide is not naturally processed and bound to the target MHC class I molecule of interest, thus allowing resources to be focused on the most promising vaccine candidates.
2776 15382048 The SSX2 gene encodes the tumor-specific antigen HOM-MEL-40/SSX2 expressed in a broad spectrum of tumors of different origin, against which humoral and CD8+ T-cell-mediated MHC-I-restricted responses have been demonstrated.
2777 15382048 Searching for promiscuous MHC-II-restricted peptides that might be suitable as a CD4+ stimulating vaccine for many patients, we used the SYFPEITHI algorithm and identified a HOM-MEL-40/SSX2-derived pentadecamer epitope (p45-59) that induced specific CD4+ T-cell responses restricted by the HLA-DRB1 subtypes *0701, *1101 and *1302 that have a cumulative prevalence of approximately 25% in the Caucasian population.
2778 15382048 No correlation was found between CD4+ T-cell responses against p45-59 reactivity and anti-SSX2 antibody titers in the serum of patients, suggesting that CD4+ and B-cell responses are regulated independently. p45-59 holds promise as a broadly applicable peptide vaccine for patients with SSX2-positive neoplasms.
2779 15382068 A novel DNA methyltransferase I-derived peptide eluted from soluble HLA-A*0201 induces peptide-specific, tumor-directed cytotoxic T cells.
2780 15383568 To compare the utility of these approaches, HLA-A*0201 transgenic mice were genetically immunized with plasmids encoding wild-type (wt) gag-pol, codon-optimized (CO) gag-pol, and an expression library immunization (ELI) vaccine genetically re-engineered to express non-CO fragments of gag and pol fused to ubiquitin for proteasome targeting.
2781 15383568 Equimolar delivery of each vaccine into HLA-A*0201 transgenic mice generated CD8 T cell responses, with the ELI vaccine producing up to 10-fold higher responses than the wt or CO gag-pol plasmids against cognate and mutant epitopes.
2782 15383568 To compare the utility of these approaches, HLA-A*0201 transgenic mice were genetically immunized with plasmids encoding wild-type (wt) gag-pol, codon-optimized (CO) gag-pol, and an expression library immunization (ELI) vaccine genetically re-engineered to express non-CO fragments of gag and pol fused to ubiquitin for proteasome targeting.
2783 15383568 Equimolar delivery of each vaccine into HLA-A*0201 transgenic mice generated CD8 T cell responses, with the ELI vaccine producing up to 10-fold higher responses than the wt or CO gag-pol plasmids against cognate and mutant epitopes.
2784 15383595 Ten epitopic regions were identified across p17, p24, and p2p7p1p6, and greater than two-thirds of targeted regions were directed at: TGTEELRSLYNTVATLY (p17, 35%); GPKEPFRDYVDRFFKTLRAEQATQDV (p24, 19%); and RGGKLDKWEKIRLRPGGKKHYMLKHL (p17, 15%).
2785 15383595 Fine epitope mapping revealed that five of nine identified optimal Gag epitopes were novel: HLVWASREL, LVWASRELERF, LYNTVATLY, PFRDYVDRFF, and TLRAEQATQD, and were restricted by unique HLA-Cw*08, HLA-A*30/B*57, HLA-A*29/B*44, and HLA-Cw*03 alleles, respectively.
2786 15389286 Immunological properties and vaccine efficacy of murine dendritic cells simultaneously expressing melanoma-associated antigen and interleukin-12.
2787 15389286 In the present study, in order to create a dendritic cell (DC)-based vaccine capable of positively skewing immune response toward a cellular immunity-dominant state, we analyzed immunological characteristics and vaccine efficacy of DCs cotransduced with melanoma-associated antigen (gp100) and IL-12 gene (gp100+IL12/DCs) by using RGD fiber-mutant adenovirus vector (AdRGD), which enables highly efficient gene transduction into DCs. gp100+IL12/DCs could simultaneously express cytoplasmic gp100 and secretory IL-12 at levels comparable to DCs transduced with each gene alone.
2788 15389286 In comparison with DCs transduced with gp100 alone (gp100/DCs), upregulation of major histocompatibility complex class I, CD40, and CD86 molecules on the cell surface and more potent T-cell-stimulating ability for proliferation and interferon-gamma secretion were observed as characteristic changes in gp100+IL12/DCs.
2789 15389286 In addition, administration of gp100+IL12/DCs, which were prepared by a relatively low dose of AdRGD-IL12, could induce more potent tumor-specific cellular immunity in the murine B16BL6 melanoma model than vaccination with gp100/DCs.
2790 15389286 However, antitumor effect and B16BL6-specific cytotoxic T-lymphocyte activity in mice vaccinated with gp100+IL12/DCs diminished with increasing AdRGD-IL12 dose during gene transduction, and paralleled the decrease in presentation levels via MHC class I molecules for antigen transduced with another AdRGD.
2791 15448372 Identification of novel HLA-A*0201-restricted CD8+ T-cell epitopes on hepatitis delta virus.
2792 15448372 Following HDV DNA vaccination, nearly 0.9 % of the total splenic CD8+ T cells were specific for peptides HDV 26-34 and HDV 43-51 in HLA-A*0201 transgenic mice, which was significantly higher than the number found in non-transgenic mice or in transgenic mice that had been immunized with control plasmid.
2793 15448372 Identification of novel HLA-A*0201-restricted CD8+ T-cell epitopes on hepatitis delta virus.
2794 15448372 Following HDV DNA vaccination, nearly 0.9 % of the total splenic CD8+ T cells were specific for peptides HDV 26-34 and HDV 43-51 in HLA-A*0201 transgenic mice, which was significantly higher than the number found in non-transgenic mice or in transgenic mice that had been immunized with control plasmid.
2795 15449035 The (MHC class I-restricted) peptides were from gp100, MART-1, tyrosinase, and MAGE-3.
2796 15449035 The gp100 and MART-1 peptides had been modified to increase their immunogenicity.
2797 15453955 We describe a hypothetical alternative to the standard artificial tetramer assay, that has the potential to detect CD4+ and CD8+ T-lymphocytes that react with any peptides expressed in the context of HLA-class I or HLA-class II.
2798 15456078 We found that lipopolysaccharides (LPS), unmethylated CpG motifs (CpG ODN) and sorbitol enhanced CVLP-induced stimulation of C57BL/6 mouse BMDCs as revealed by increased levels of CD40, CD80, MHC II and CD54 at the cell surface.
2799 15470050 As a result, these two molecules account for virtually all known MHC class I-restricted SIV-derived CD8+ T cell epitopes.
2800 15470050 The synthesis of five Mamu-A*02 tetramers demonstrated the discrepancy between tetramer binding and IFN-gamma secretion by SIV-specific CD8+ T cells during chronic SIV infection.
2801 15494539 Identification of a human HLA-E-restricted CD8+ T cell subset in volunteers immunized with Salmonella enterica serovar Typhi strain Ty21a typhoid vaccine.
2802 15494539 Typhi-infected targets regardless of whether they share classical HLA class I molecules with them, by a FAS-independent, granule-dependent mechanism, as evidenced by induction of granzyme B release and the blocking effects of concanamycin and strontium ions.
2803 15494539 The expression of HLA-E Ags, but not CD1-a, -b, or -c, on the membrane of S.
2804 15494539 Typhi Ags via HLA-E could stimulate IFN-gamma production.
2805 15494539 Typhi GroEL HLA-E binding motifs.
2806 15494539 These results demonstrate that HLA-E binds nonamer peptides derived from bacterial proteins and trigger CD8+-mediated lysis and IFN-gamma production when exposed to infected targets, raising the possibility that this novel effector mechanism might contribute to host defense against intracellular bacterial infections.
2807 15520206 Previously, we demonstrated that radiation increased Fas (CD95) gene expression in carcinoembryonic antigen (CEA)-expressing murine tumor cells, which consequently enhanced their susceptibility to CEA-specific CTL-mediated killing.
2808 15520206 Seventy-two hours postirradiation, changes in surface expression of Fas (CD95), as well as expression of other surface molecules involved in T-cell-mediated immune attack such as intercellular adhesion molecule 1, mucin-1, CEA, and MHC class I, were examined.
2809 15520206 Furthermore, five of five irradiated CEA(+)/A2(+) colon tumor cells lines demonstrated significantly enhanced killing by CEA-specific HLA-A2-restricted CD8(+) CTLs compared with nonirradiated counterparts.
2810 15528326 Cutting edge: cross-presentation of cell-associated antigens to MHC class I molecule is regulated by a major transcription factor for heat shock proteins.
2811 15528326 The ability for the professional APC to cross-present Ag to MHC class I from parenchymal cells is essential for priming as well as tolerance of CD8+ T cells against intracellular Ags.
2812 15528326 We herein genetically addressed this hypothesis using mice that were defective of heat shock factor 1 (Hsf1), a major transcription factor for HSPs.
2813 15528326 Hsf1(-/-) mice have a decreased expression of several HSPs including HSP90 and HSP70.
2814 15528326 Using multiple Ag systems, we demonstrated that cross-priming of Ag-specific CD8+ T cells was inefficient when Ag expression was restricted to Hsf1(-/-) non-APCs.
2815 15528326 Our study provides the first genetic evidence for the roles of Hsf1 in regulating cross-presentation of MHC class I-associated Ags.
2816 15528326 Cutting edge: cross-presentation of cell-associated antigens to MHC class I molecule is regulated by a major transcription factor for heat shock proteins.
2817 15528326 The ability for the professional APC to cross-present Ag to MHC class I from parenchymal cells is essential for priming as well as tolerance of CD8+ T cells against intracellular Ags.
2818 15528326 We herein genetically addressed this hypothesis using mice that were defective of heat shock factor 1 (Hsf1), a major transcription factor for HSPs.
2819 15528326 Hsf1(-/-) mice have a decreased expression of several HSPs including HSP90 and HSP70.
2820 15528326 Using multiple Ag systems, we demonstrated that cross-priming of Ag-specific CD8+ T cells was inefficient when Ag expression was restricted to Hsf1(-/-) non-APCs.
2821 15528326 Our study provides the first genetic evidence for the roles of Hsf1 in regulating cross-presentation of MHC class I-associated Ags.
2822 15528326 Cutting edge: cross-presentation of cell-associated antigens to MHC class I molecule is regulated by a major transcription factor for heat shock proteins.
2823 15528326 The ability for the professional APC to cross-present Ag to MHC class I from parenchymal cells is essential for priming as well as tolerance of CD8+ T cells against intracellular Ags.
2824 15528326 We herein genetically addressed this hypothesis using mice that were defective of heat shock factor 1 (Hsf1), a major transcription factor for HSPs.
2825 15528326 Hsf1(-/-) mice have a decreased expression of several HSPs including HSP90 and HSP70.
2826 15528326 Using multiple Ag systems, we demonstrated that cross-priming of Ag-specific CD8+ T cells was inefficient when Ag expression was restricted to Hsf1(-/-) non-APCs.
2827 15528326 Our study provides the first genetic evidence for the roles of Hsf1 in regulating cross-presentation of MHC class I-associated Ags.
2828 15530672 Injection of a mixture of the synthetic HPV16-E7 protein and the synthetic adjuvant CpG in mice resulted in strong functional HPV16-specific cytotoxic T-lymphocyte responses as measured by CD8+ MHC class I-tetramer staining, the detection of antigen-specific intracellular IFNgamma production and the ability to protect mice against a challenge with HPV16-E7+ TC-1 tumour cells in both prophylactic and therapeutic vaccination regimens.
2829 15531030 Incubation of immature human PBMC-derived DCs with SHIV VLPs for 48 h resulted in the significant up-regulation of CD40, CD80, CD83, CD54, CD86, HLA-A, B, C and HLA-DR, DP, DQ molecules on activated DC CD11c+ subpopulations.
2830 15531030 SHIV VLPs efficiently stimulated DCs to release IL-12, IFN-gamma and TNF-alpha.
2831 15534491 Immunization of HLA-A*0201 and/or HLA-DPbeta1*04 patients with metastatic melanoma using epitopes from the NY-ESO-1 antigen.
2832 15534491 To test whether provision of "help" would enhance antitumor immunity, the authors initiated a clinical trial in which patients with metastatic melanoma were immunized against the NY-ESO-1 tumor antigen, using an HLA-A2-restricted peptide (ESO-1:165V), an HLA-DP4-restricted peptide (NY-ESO-1:161-180), or both peptides given concomitantly.
2833 15534491 Concomitant vaccination with the HLA class II-restricted peptide did not alter the immune response to the HLA class I-restricted peptide form NY-ESO-1.
2834 15534491 Immunization of HLA-A*0201 and/or HLA-DPbeta1*04 patients with metastatic melanoma using epitopes from the NY-ESO-1 antigen.
2835 15534491 To test whether provision of "help" would enhance antitumor immunity, the authors initiated a clinical trial in which patients with metastatic melanoma were immunized against the NY-ESO-1 tumor antigen, using an HLA-A2-restricted peptide (ESO-1:165V), an HLA-DP4-restricted peptide (NY-ESO-1:161-180), or both peptides given concomitantly.
2836 15534491 Concomitant vaccination with the HLA class II-restricted peptide did not alter the immune response to the HLA class I-restricted peptide form NY-ESO-1.
2837 15542207 DNA and low titer, helper-free, recombinant AAV prime-boost vaccination for cytomegalovirus induces an immune response to CMV-pp65 and CMV-IE1 in transgenic HLA A*0201 mice.
2838 15542207 Simultaneous immunization of both CMV proteins, using DNA vaccine priming followed by rAAV boost, induced antibody (Ab) response, CD8 lymphocytes with cytotoxic function, and detectible binding of the cognate peptide epitopes for human HLA A*0201 restriction using tetramer technology.
2839 15542207 DNA and low titer, helper-free, recombinant AAV prime-boost vaccination for cytomegalovirus induces an immune response to CMV-pp65 and CMV-IE1 in transgenic HLA A*0201 mice.
2840 15542207 Simultaneous immunization of both CMV proteins, using DNA vaccine priming followed by rAAV boost, induced antibody (Ab) response, CD8 lymphocytes with cytotoxic function, and detectible binding of the cognate peptide epitopes for human HLA A*0201 restriction using tetramer technology.
2841 15542368 Antigen recognition by cytotoxic CD8 T cells is dependent upon a number of critical steps in MHC class I antigen processing including proteosomal cleavage, TAP transport into the endoplasmic reticulum, and MHC class I binding.
2842 15546948 Here we report that the type of human DC, the mode of activation, and the strategy for delivery of antigen are 3 critical factors for efficient stimulation of tumor-specific CD8+ and CD4+ T cells.
2843 15546948 Only CD1c+ blood DCs and monocyte-derived DCs (MoDCs) were capable of presenting epitopes of the full-length tumor antigen NY-ESO-1 on both major histocompatibility complex (MHC) class I (cross-presentation) and MHC II, whereas plasmacytoid DCs were limited to MHC II presentation.
2844 15557175 Transporter associated with antigen processing preselection of peptides binding to the MHC: a bioinformatic evaluation.
2845 15557759 These altered HLA class I phenotypes and non-ubiquitous expression of NK receptor ligands constitute the major tumor escape mechanism facing tumor-specific CTL and/or NK cell mediated responses.
2846 15560980 Enforced endocytosis of Ag together with the adjuvant effect of Toll-like receptor 9 ligands might be key for the efficient cross-presentation of exogeneous Ag as well as for effective cross-priming of MHC class I restricted CD8 T effector cells.
2847 15565183 Intratumoral administration of immature dendritic cells following the adenovirus vector encoding CD40 ligand elicits significant regression of established myeloma.
2848 15565183 The potent antitumor effect produced by the combination therapy correlated with high expression of MHC, costimulatory and Fas molecules on J558 cells, which was derived from CD40L transgene expression.
2849 15565183 Finally, in vivo depletion experimentation suggested both CD4+ and CD8+ T cells were involved in mediating the antitumor immune responses of combined treatment of AdVCD40L and iDCs, with CD8+ T cells being the major effector.
2850 15576418 Enhanced presentation of the Ckappa epitope was most likely a result of increased loading of MHC class II molecules, as the CD14-specific monoclonal Ab 3C10 did not induce maturation of the APC.
2851 15585916 The vaccine may use major histocompatibility complex (MHC) class I- or class II-restricted peptides to elicit stimulation of CD8+ cytotoxic T-lymphocytes (CTL) or CD4+ T-helper cells, respectively.
2852 15585926 Since the method is not restricted to any antigen or major histocompatibility complex (MHC) haplotype, it enables us to detect CD8+ as well as CD4+ T-cells reacting against a wide vary of tumor-associated antigens, ranging from particular known tumor antigens to whole tumor cells and crude tumor lysates.
2853 15592417 The extreme polymorphism in the human leukocyte antigen (HLA) class I region of the human genome is suggested to provide an advantage in pathogen defence mediated by CD8+ T cells.
2854 15592417 HLA class I molecules present pathogen-derived peptides on the surface of infected cells for recognition by CD8+ T cells.
2855 15592417 In 375 HIV-1-infected study subjects from southern Africa, a significantly greater number of CD8+ T-cell responses are HLA-B-restricted, compared to HLA-A (2.5-fold; P = 0.0033).
2856 15592417 Here we show that variation in viral set-point, in absolute CD4 count and, by inference, in rate of disease progression in the cohort, is strongly associated with particular HLA-B but not HLA-A allele expression (P < 0.0001 and P = 0.91, respectively).
2857 15592417 Moreover, substantially greater selection pressure is imposed on HIV-1 by HLA-B alleles than by HLA-A (4.4-fold, P = 0.0003).
2858 15592417 The extreme polymorphism in the human leukocyte antigen (HLA) class I region of the human genome is suggested to provide an advantage in pathogen defence mediated by CD8+ T cells.
2859 15592417 HLA class I molecules present pathogen-derived peptides on the surface of infected cells for recognition by CD8+ T cells.
2860 15592417 In 375 HIV-1-infected study subjects from southern Africa, a significantly greater number of CD8+ T-cell responses are HLA-B-restricted, compared to HLA-A (2.5-fold; P = 0.0033).
2861 15592417 Here we show that variation in viral set-point, in absolute CD4 count and, by inference, in rate of disease progression in the cohort, is strongly associated with particular HLA-B but not HLA-A allele expression (P < 0.0001 and P = 0.91, respectively).
2862 15592417 Moreover, substantially greater selection pressure is imposed on HIV-1 by HLA-B alleles than by HLA-A (4.4-fold, P = 0.0003).
2863 15592417 The extreme polymorphism in the human leukocyte antigen (HLA) class I region of the human genome is suggested to provide an advantage in pathogen defence mediated by CD8+ T cells.
2864 15592417 HLA class I molecules present pathogen-derived peptides on the surface of infected cells for recognition by CD8+ T cells.
2865 15592417 In 375 HIV-1-infected study subjects from southern Africa, a significantly greater number of CD8+ T-cell responses are HLA-B-restricted, compared to HLA-A (2.5-fold; P = 0.0033).
2866 15592417 Here we show that variation in viral set-point, in absolute CD4 count and, by inference, in rate of disease progression in the cohort, is strongly associated with particular HLA-B but not HLA-A allele expression (P < 0.0001 and P = 0.91, respectively).
2867 15592417 Moreover, substantially greater selection pressure is imposed on HIV-1 by HLA-B alleles than by HLA-A (4.4-fold, P = 0.0003).
2868 15592417 The extreme polymorphism in the human leukocyte antigen (HLA) class I region of the human genome is suggested to provide an advantage in pathogen defence mediated by CD8+ T cells.
2869 15592417 HLA class I molecules present pathogen-derived peptides on the surface of infected cells for recognition by CD8+ T cells.
2870 15592417 In 375 HIV-1-infected study subjects from southern Africa, a significantly greater number of CD8+ T-cell responses are HLA-B-restricted, compared to HLA-A (2.5-fold; P = 0.0033).
2871 15592417 Here we show that variation in viral set-point, in absolute CD4 count and, by inference, in rate of disease progression in the cohort, is strongly associated with particular HLA-B but not HLA-A allele expression (P < 0.0001 and P = 0.91, respectively).
2872 15592417 Moreover, substantially greater selection pressure is imposed on HIV-1 by HLA-B alleles than by HLA-A (4.4-fold, P = 0.0003).
2873 15592417 The extreme polymorphism in the human leukocyte antigen (HLA) class I region of the human genome is suggested to provide an advantage in pathogen defence mediated by CD8+ T cells.
2874 15592417 HLA class I molecules present pathogen-derived peptides on the surface of infected cells for recognition by CD8+ T cells.
2875 15592417 In 375 HIV-1-infected study subjects from southern Africa, a significantly greater number of CD8+ T-cell responses are HLA-B-restricted, compared to HLA-A (2.5-fold; P = 0.0033).
2876 15592417 Here we show that variation in viral set-point, in absolute CD4 count and, by inference, in rate of disease progression in the cohort, is strongly associated with particular HLA-B but not HLA-A allele expression (P < 0.0001 and P = 0.91, respectively).
2877 15592417 Moreover, substantially greater selection pressure is imposed on HIV-1 by HLA-B alleles than by HLA-A (4.4-fold, P = 0.0003).
2878 15609328 Analysis of exosomes purified from these cells revealed that exosomes contained the target MUC1 antigen on their surfaces as well as other well-described exosomal proteins, including Hsc70 and MHC class I molecules.
2879 15613296 The identification of this common M. nemestrina MHC class I allele restricting a functionally important immunodominant SIV Gag epitope establishes a basis for studying CD8+ T-cell responses against AIDS in an important, widely available nonhuman primate species.
2880 15627214 The responses to the viral vector, to known HLA class I-restricted tyrosinase peptides, and to dendritic cells transfected with tyrosinase mRNA, were investigated by ELISpot assay on both ex vivo T cells and on T cells stimulated in vitro prior to testing.
2881 15627214 A strong response to the viral vector was achieved, indicated by an increase in the frequency of MVA-specific CD4+ and CD8+ T cells and an increase in virus-specific antibody titers.
2882 15650058 Molecular modification of idiotypes from B-cell lymphomas for expression in mature dendritic cells as a strategy to induce tumor-reactive CD4+ and CD8+ T-cell responses.
2883 15650058 This study exploited a molecular approach to modify the Id of 38C13 lymphoma for processing via class I and II antigen-processing pathways and evaluated protein expression in dendritic cells (DCs) to simultaneously stimulate tumor reactive CD8(+) and CD4(+) lymphocytes.
2884 15650058 Recombinant vaccinia viruses (rVVs) were constructed, coding for Id fused with the targeting signal of the lysosomal-associated membrane protein1 (Id-LAMP1) to promote antigen presentation in the context of major histocompatibility complex (MHC) class II.
2885 15650058 Mature DCs infected with rVV/Id-LAMP1 elicited both CD4(+) and CD8(+) Id-specific T cells and protected animals from tumor challenge.
2886 15650058 Id-specific CD8(+) cells were required to mediate the effector phase of a therapeutic response, and CD4(+) cells were beneficial in the induction phase of the response.
2887 15650058 These results demonstrate that fusing Id to LAMP1 enhances CD8(+) and CD4(+) Id-specific responses for NHLs and may be useful therapeutically.
2888 15650233 Here we shall review the work carried out in our lab in recent years and show that NB cells express tumor-associated antigens, such as MAGE-3, but lack constitutive expression of costimulatory molecules and surface HLA class I and II molecules.
2889 15650233 Notably, in vitro experiments with NB cell lines demonstrated that surface HLA class I molecules and the CD40 costimulatory molecule were upregulated following cell incubation with recombinant interferon-gamma.
2890 15650233 Interaction of CD40 with recombinant CD40 ligand induced apoptosis of NB cells through a caspase 8-dependent mechanism.
2891 15650233 Here we shall review the work carried out in our lab in recent years and show that NB cells express tumor-associated antigens, such as MAGE-3, but lack constitutive expression of costimulatory molecules and surface HLA class I and II molecules.
2892 15650233 Notably, in vitro experiments with NB cell lines demonstrated that surface HLA class I molecules and the CD40 costimulatory molecule were upregulated following cell incubation with recombinant interferon-gamma.
2893 15650233 Interaction of CD40 with recombinant CD40 ligand induced apoptosis of NB cells through a caspase 8-dependent mechanism.
2894 15660789 Gross pathology, histology, immunohistochemistry using antisera against major histocompatibility complex (MHC) class II beta chain and transmission electron microscopy (TEM) were used to characterize the changes.
2895 15661141 The LAMP sequences are used to direct the antigen protein to the major histocompatibility class II (MHC II) vesicular compartment of transfected professional antigen-presenting cells (APCs).
2896 15661141 Additionally, confocal and immunoelectron microscopic analyses of transfected B cells showed localization of the WN preM-E/LAMP chimera in vesicular compartments containing endogenous LAMP, MHC II, and H2-M, whereas native viral preM-E lacking the LAMP sequences was distributed within the cellular vesicular network with little LAMP or MHC II association.
2897 15661141 These results underscore the utility of LAMP targeting of the WN envelope to the MHC II compartments in the design of a genetic WN vaccine.
2898 15661141 The LAMP sequences are used to direct the antigen protein to the major histocompatibility class II (MHC II) vesicular compartment of transfected professional antigen-presenting cells (APCs).
2899 15661141 Additionally, confocal and immunoelectron microscopic analyses of transfected B cells showed localization of the WN preM-E/LAMP chimera in vesicular compartments containing endogenous LAMP, MHC II, and H2-M, whereas native viral preM-E lacking the LAMP sequences was distributed within the cellular vesicular network with little LAMP or MHC II association.
2900 15661141 These results underscore the utility of LAMP targeting of the WN envelope to the MHC II compartments in the design of a genetic WN vaccine.
2901 15661141 The LAMP sequences are used to direct the antigen protein to the major histocompatibility class II (MHC II) vesicular compartment of transfected professional antigen-presenting cells (APCs).
2902 15661141 Additionally, confocal and immunoelectron microscopic analyses of transfected B cells showed localization of the WN preM-E/LAMP chimera in vesicular compartments containing endogenous LAMP, MHC II, and H2-M, whereas native viral preM-E lacking the LAMP sequences was distributed within the cellular vesicular network with little LAMP or MHC II association.
2903 15661141 These results underscore the utility of LAMP targeting of the WN envelope to the MHC II compartments in the design of a genetic WN vaccine.
2904 15665097 The highly polymorphic gene products of the classical MHC class I genes in humans (HLA-A, HLA-B, and HLA-C) play a critical role in the immune defense against intracellular infections.
2905 15688345 This vaccine induced strong CD8(+), CD4(+) T lymphocyte and antibody responses specific for the immunizing peptide.
2906 15688345 CD8(+) T lymphocyte responses elicited in HLA-A*0201 volunteers recognized two well-defined cytotoxic T lymphocyte epitopes within the CS.
2907 15694996 HLA A*0301- and HLA A*6801-restricted CD8+ pp150 T-cell clones derived from different donors were found to efficiently kill autologous CMV-infected fibroblasts.
2908 15699107 Vaccine efficacy is due to direct presentation of endogenously synthesized, MHC II-restricted tumor peptides to CD4+ T cells.
2909 15699142 Membrane-anchored beta 2-microglobulin stabilizes a highly receptive state of MHC class I molecules.
2910 15705424 Furthermore, we provide a critical assessment of the studies that examine the mechanisms controlling DC MHC class II antigen presentation, which have often reached contradictory conclusions.
2911 15705910 Diverse CD8+ T-cell responses to renal cell carcinoma antigens in patients treated with an autologous granulocyte-macrophage colony-stimulating factor gene-transduced renal tumor cell vaccine.
2912 15705910 A phase I clinical trial with granulocyte-macrophage colony-stimulating factor tumor cell vaccines in patients with metastatic renal cell carcinoma (RCC) showed immune cell infiltration at vaccine sites and delayed-type hypersensitivity (DTH) responses to autologous tumor cells indicative of T-cell immunity.
2913 15705910 A third line recognized a unique HLA-A*0101-restricted RCC antigen derived from a mutated KIAA1440 gene specific to the tumor.
2914 15705910 In addition, two independent CTL lines and three clones were also generated from patient 26 and they recognized autologous tumor cells restricted through HLA-A*0205, HLA-A/B/C, and HLA-B/C.
2915 15705910 These results show that paracrine granulocyte-macrophage colony-stimulating factor tumor vaccines may generate a diverse repertoire of tumor-reactive CD8+ T-cell responses and emphasize the importance of polyvalency in the design of cancer immunotherapies.
2916 15705910 Diverse CD8+ T-cell responses to renal cell carcinoma antigens in patients treated with an autologous granulocyte-macrophage colony-stimulating factor gene-transduced renal tumor cell vaccine.
2917 15705910 A phase I clinical trial with granulocyte-macrophage colony-stimulating factor tumor cell vaccines in patients with metastatic renal cell carcinoma (RCC) showed immune cell infiltration at vaccine sites and delayed-type hypersensitivity (DTH) responses to autologous tumor cells indicative of T-cell immunity.
2918 15705910 A third line recognized a unique HLA-A*0101-restricted RCC antigen derived from a mutated KIAA1440 gene specific to the tumor.
2919 15705910 In addition, two independent CTL lines and three clones were also generated from patient 26 and they recognized autologous tumor cells restricted through HLA-A*0205, HLA-A/B/C, and HLA-B/C.
2920 15705910 These results show that paracrine granulocyte-macrophage colony-stimulating factor tumor vaccines may generate a diverse repertoire of tumor-reactive CD8+ T-cell responses and emphasize the importance of polyvalency in the design of cancer immunotherapies.
2921 15709165 Our data suggest that Livin/ML-IAP may be an excellent target antigen in immunotherapy for lung cancer and Livin7 peptide may serve as a potent peptide vaccine for HLA-A*2402(+)/Livin(+) lung cancer patients.
2922 15710457 Corticosterone impairs MHC class I antigen presentation by dendritic cells via reduction of peptide generation.
2923 15720438 A soluble LAG-3 (CD223) molecule (sLAG-3) is a natural, high-affinity ligand for MHC class II.
2924 15720438 It is known to induce maturation of monocyte-derived dendritic cells in vitro and is used as a vaccine adjuvant to induce CD4 T helper type 1 responses and CD8 T-cell responses in vivo.
2925 15720438 Here, we demonstrate that sLAG-3 (but not an MHC class II-specific monoclonal antibody) reduces the differentiation of monocytes into macrophages in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) as well as their differentiation into dendritic cells in the presence of GM-CSF and interleukin-4, as shown by a decrease in CD14 and CD1a expression, respectively.
2926 15720438 A soluble LAG-3 (CD223) molecule (sLAG-3) is a natural, high-affinity ligand for MHC class II.
2927 15720438 It is known to induce maturation of monocyte-derived dendritic cells in vitro and is used as a vaccine adjuvant to induce CD4 T helper type 1 responses and CD8 T-cell responses in vivo.
2928 15720438 Here, we demonstrate that sLAG-3 (but not an MHC class II-specific monoclonal antibody) reduces the differentiation of monocytes into macrophages in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) as well as their differentiation into dendritic cells in the presence of GM-CSF and interleukin-4, as shown by a decrease in CD14 and CD1a expression, respectively.
2929 15725960 Boosting vaccinations with peptide-pulsed CD34+ progenitor-derived dendritic cells can expand long-lived melanoma peptide-specific CD8+ T cells in patients with metastatic melanoma.
2930 15725960 The authors showed earlier, in 18 HLA-A*0201 metastatic melanoma patients, that four vaccinations over 6 weeks with peptide-loaded CD34-DCs (the induction phase) expand in the blood melanoma-specific CD8+ T cells, as documented by melanoma peptide-specific IFN-gamma ELISPOT and cytotoxic T-lymphocyte (CTL) activity against melanoma cell lines.
2931 15728523 MAGE-A1-, MAGE-A10-, and gp100-derived peptides are immunogenic when combined with granulocyte-macrophage colony-stimulating factor and montanide ISA-51 adjuvant and administered as part of a multipeptide vaccine for melanoma.
2932 15728523 We report in this study that at least three of these five peptides (MAGE-A1(96-104), MAGE-A10(254-262), and gp100(614-622)) are immunogenic when administered with GM-CSF in Montanide ISA-51 adjuvant.
2933 15728523 Most importantly, tumor cell lines expressing the appropriate HLA-A restriction element and MAGE-A1, MAGE-A10, or gp100 proteins were lysed by corresponding CTL.
2934 15728523 This report supports the continued use of the MAGE-A1(96-104), MAGE-A10(254-262), and gp100(614-622) epitopes in peptide-based melanoma vaccines and thus expands the list of immunogenic peptide Ags available for human use.
2935 15728523 Cancer-testis Ags are expressed in multiple types of cancer; thus the MAGE-A1(96-104) and MAGE-A10(254-262) peptides may be considered for inclusion in vaccines against cancers of other histologic types, in addition to melanoma.
2936 15729696 Several MUC1-derived peptides binding HLA-A*0201 molecules have been identified that correspond to sequences outside the tandem repeat.
2937 15731029 In whole tachyzoite antigen-expanded bovine T-lymphocyte lines, recombinant NcSRS2 induced potent memory CD4+- and CD8+-T-lymphocyte activation, as indicated by proliferation and gamma interferon (IFN-gamma) secretion, while recombinant NcSAG1 induced a minimal memory response.
2938 15731029 These findings support investigation of subunit N. caninum vaccines incorporating NcSRS2 gene sequences or peptides for induction of NcSRS2 peptide-specific CTL and IFN-gamma-secreting T lymphocytes in cattle with varied MHC genotypes.
2939 15731055 DC exposed to live EBs acquired a mature DC morphology; expressed high levels of major histocompatibility complex (MHC) class II, CD80, CD86, CD40, and ICAM-1; produced elevated amounts of interleukin-12 and tumor necrosis factor alpha; and were efficiently recognized by Chlamydia-specific CD4+ T cells.
2940 15731055 In contrast, UV-EB-pulsed DC expressed low levels of CD40 and CD86 but displayed high levels of MHC class II, ICAM-1, and CD80; secreted low levels of proinflammatory cytokines; and exhibited reduced recognition by Chlamydia-specific CD4+ T cells.
2941 15731055 DC exposed to live EBs acquired a mature DC morphology; expressed high levels of major histocompatibility complex (MHC) class II, CD80, CD86, CD40, and ICAM-1; produced elevated amounts of interleukin-12 and tumor necrosis factor alpha; and were efficiently recognized by Chlamydia-specific CD4+ T cells.
2942 15731055 In contrast, UV-EB-pulsed DC expressed low levels of CD40 and CD86 but displayed high levels of MHC class II, ICAM-1, and CD80; secreted low levels of proinflammatory cytokines; and exhibited reduced recognition by Chlamydia-specific CD4+ T cells.
2943 15753402 Although nonresponsive toward the HPV16 E7 oncoprotein in the CD8+ T-cell compartment by virtue of MHC haplotype, the mice were capable of mounting an induced CD4+ T-cell response against E7, and in addition developed spontaneous anti-E7 antibodies.
2944 15755572 CD4 and CD8 lymphocyte counts did not change significantly among volunteers.
2945 15755572 CD8 MHC class I-restricted responses to HIV antigens were assayed.
2946 15787742 Murine bone marrow-derived dendritic cells (DC) can be generated by culture in the presence of granulocyte/macrophage colony-stimulating factor (GM-CSF) alone or GM-CSF in conjunction with interleukin-4 (IL-4).
2947 15787742 Also, the four culture conditions generated CD11c+ DC with comparable levels of major histocompatibility complex (MHC) class II, CD40, CD80 and CD86 expression, with the exception of cells cultured under serum-free conditions in the absence of IL-4, which displayed suboptimal levels of these markers.
2948 15787742 However, both DC populations displayed a similar capacity to take up fluorescein isothiocyanate (FITC)-albumin by macropinocytosis and FITC-Dextran by the mannose receptor and to secrete IL-12 in response to stimulation with lipopolysaccharide (LPS) or an agonistic anti-CD40 monoclonal antibody.
2949 15787742 Therefore, we conclude that although both DC culture methods result in the production of DC with similar functional abilities, under serum-free conditions, DC cultured in GM-CSF and IL-4 show an increased stimulatory potential over DC cultured in GM-CSF alone.
2950 15797470 We generated a mammalian expression system for recombinant cytokines using the equine IgG1 heavy chain constant region as a tag for detection and purification of the expressed cytokine, demonstrated here using equine interferon-gamma (IFN-gamma), interleukin-2 (IL-2), interleukin-4 (IL4) and transforming growth factor-beta1 (TGF-beta1).
2951 15797470 The purification of the fusion protein by protein G affinity columns, the enterokinase digestion of the cytokine from the IgG1 heavy chain region after or during purification, and the biological activity of the cytokine within the fusion protein or after its isolation was demonstrated in detail for equine IFN-gamma/IgG1 by up-regulation of major histocompatibility complex (MHC) class II expression on horse lymphocytes.
2952 15797470 Biological activity could also be confirmed for the IL-2 and IL-4/IgG1 fusion proteins.
2953 15797470 To test the crossreactivity and specificity of anti-human TGF-beta1, and anti-bovine and anti-canine IFN-gamma antibodies to respective horse cytokines, the four cytokine/IgG1 fusion proteins were successfully used in ELISA, flow cytometry and/or Western blotting.
2954 15803143 To augment their nonspecific immunogenic properties, before DNA transfer, the fibroblasts (of C3H/He mouse origin) were modified to express allogeneic MHC class I H-2Kb-determinants and to secrete IL-2, IL-18 or GM-CSF.
2955 15803143 The immunotherapeutic properties of transfected fibroblasts modified to secrete IL-18 or GM-CSF were less efficacious.
2956 15814688 To test whether simple expression units used in DNA vaccines can generate immunogenic, MHC class I-binding epitopes by translating other than the primary open reading frame (ORF), we constructed a vector (pCI/SX) that encodes the small hepatitis B surface Ag in the primary ORF, and a C-terminal fragment (residue 344-832) of the polymerase (Pol) in an alternative (out-of-frame) reading frame. pCI/SX efficiently primed multispecific, HLA-A2-restricted CD8+ T cell responses to epitopes of hepatitis B surface Ag and of Pol (Pol3, Pol(803-811)).
2957 15824323 This approach may be broadly improved by targeting the MHC class I chain-related protein A (MICA), which is frequently and abundantly expressed on most if not all types of epithelial cancers but not in normal tissues except intestinal mucosa.
2958 15824323 Loading of DC with anti-MICA mAb-coated breast, melanoma, or ovarian tumor lines or uncultured ovarian cancer cells efficiently promoted TA cross-presentation and priming of multivalent anti-tumor CD8 and CD4 T cell responses.
2959 15843436 We improved an existing vaccine platform based on immunopotentiating reconstituted influenza virosomes (IRIVs) for efficient delivery of peptide epitopes to the MHC class I antigen presentation pathway.
2960 15843519 Although endocytosed proteins are commonly presented via the class II MHC pathway to stimulate CD4(+) T cells, professional APCs can also cross-present Ags, whereby these exogenous peptides can be complexed with class I MHC for cross-priming of CD8(+) T cells.
2961 15843563 This mass tag-assisted approach provides a useful methodology for rapid identification of MHC class II presented bacterial CD4(+) T cell epitopes relevant for vaccine development.
2962 15843575 Recently we reported that Cpn-infected mice generate an MHC class I-restricted CD8(+) Tc1 response against various Cpn Ags, and that CD8(+) CTL to multiple epitopes inhibit Cpn growth in vitro.
2963 15843575 CD8(+) T cell lines generated to minigene-encoded CTL epitopes secreted IFN-gamma and TNF-alpha and exhibited CTL activity upon recognition of Cpn-infected macrophages.
2964 15843575 Immunization and challenge studies with beta(2)-microglobulin(-/-) mice indicated that the reduction of lung Cpn burdens was mediated by the MHC class I-dependent CD8(+) T cells to minigene-included Cpn CTL epitopes, rather than by pan-DR epitope-specific CD4(+) T cells.
2965 15843575 Recently we reported that Cpn-infected mice generate an MHC class I-restricted CD8(+) Tc1 response against various Cpn Ags, and that CD8(+) CTL to multiple epitopes inhibit Cpn growth in vitro.
2966 15843575 CD8(+) T cell lines generated to minigene-encoded CTL epitopes secreted IFN-gamma and TNF-alpha and exhibited CTL activity upon recognition of Cpn-infected macrophages.
2967 15843575 Immunization and challenge studies with beta(2)-microglobulin(-/-) mice indicated that the reduction of lung Cpn burdens was mediated by the MHC class I-dependent CD8(+) T cells to minigene-included Cpn CTL epitopes, rather than by pan-DR epitope-specific CD4(+) T cells.
2968 15847794 Thus far, CD8+ T cell epitopes have been identified either using an overlapping peptide library covering an entire protein, or using algorithms designed to identify likely peptides that bind to major histocompatibility complex (MHC) class I molecules.
2969 15855013 This formulation was found to effectively elicit CD8+ cytotoxic T cell (CTL) responses in an HLA-A*0201 transgenic mouse model.
2970 15855013 Co-administration of the peptide-microspheres with adjuvants, including granulocyte-macrophage colony stimulating factor, MPL adjuvant and select synthetic Toll-Like Receptor 4 ligands, the aminoalkyl glucosaminide-4 phosphates, significantly augmented CTL responses.
2971 15857936 Enhancement of antigen acquisition by dendritic cells and MHC class II-restricted epitope presentation to CD4+ T cells using VP22 DNA vaccine vectors that promote intercellular spreading following initial transfection.
2972 15865420 Such shortening was associated with a shift in HLA-DRbeta1* molecule binding and a consequent shift in functional register reading, mainly by alleles of the same haplotype when compared with immunogenic protection-inducing HABPs, suggesting an imperfect and different conformation of the MHC II peptide-TCR complex.
2973 15879130 Activated B cells exhibited increased expression of activation markers and ligands that are critical for cross-talk with T cells (CD19, CD25, CD80, CD86, MHC I, MHC II, and CD40).
2974 15893615 Identification and characterization of HIV-1-specific CD8+ T cell epitopes presented by HLA-A*2601.
2975 15893615 The ability of these HLA-A*2601-binding peptides to induce peptide-specific CD8(+) T cells was tested by stimulating PBMCs from HIV-1-infected individuals having HLA-A*2601 with these peptides.
2976 15893615 Four HLA-A*2601-binding peptides induced peptide-specific CD8 T cells.
2977 15893615 Identification and characterization of HIV-1-specific CD8+ T cell epitopes presented by HLA-A*2601.
2978 15893615 The ability of these HLA-A*2601-binding peptides to induce peptide-specific CD8(+) T cells was tested by stimulating PBMCs from HIV-1-infected individuals having HLA-A*2601 with these peptides.
2979 15893615 Four HLA-A*2601-binding peptides induced peptide-specific CD8 T cells.
2980 15893615 Identification and characterization of HIV-1-specific CD8+ T cell epitopes presented by HLA-A*2601.
2981 15893615 The ability of these HLA-A*2601-binding peptides to induce peptide-specific CD8(+) T cells was tested by stimulating PBMCs from HIV-1-infected individuals having HLA-A*2601 with these peptides.
2982 15893615 Four HLA-A*2601-binding peptides induced peptide-specific CD8 T cells.
2983 15893699 A panel of CD4 T-cell clones was isolated from synovial fluid by single cell flow cytometry from a patient with treatment-resistant Lyme arthritis using a DRB1*0401 major histocompatibility complex (MHC) class II tetramer covalently loaded with outer surface protein A (OspA) peptide164-175, an immunodominant epitope of Borrelia burgdorferi.
2984 15916488 The proteasome degrades cellular proteins and provides peptides for major histocompatibility complex (MHC) class I molecules to drive CD8+ T-cell responses to kill intracellular pathogens.
2985 15919923 SIV Gag-specific T-cell responses were detected in peripheral blood by MHC class I tetramer staining (peak, 0.07 to 0.2% CD8(+) T cells at week 2) and gamma interferon (IFN-gamma) enzyme-linked immunospot (ELISPOT) assays (peak, 50 to 250 spot forming cells/10(6) peripheral blood mononuclear cell at week 3).
2986 15928582 With regard to HLA class I molecules, association with HLA-B was especially observed.HLA-B35 and -B8 correlated with chronic active hepatitis (CAH)and with hepatitis B carriers.
2987 15936851 In this study, we demonstrated that WKYMVm enhanced the surface expression of CD80, but not that of CD40, CD86 and MHC class II, on mouse bone marrow-derived dendritic cells which is one of the essential costimulatory signals for the induction of immune responses.
2988 15936851 Furthermore, when WKYMVm was codelivered with HIV, HBV and Influenza DNA vaccines, WKYMVm selectively enhanced the vaccine-induced CD8(+) T cell responses in a dose-dependent manner, in terms of IFN-gamma secretion and cytolytic activity.
2989 15940420 Susceptibility to HIV-1 infections is, beside other factors, determined by individual host genetic variants like HLA class I alleles, CCR5 and CCR2 variants and levels of CCR5 binding chemokines.
2990 15958679 Importantly, when monitored at the memory phase, significantly higher vaccinia virus-specific total CD8(+) and HLA-A*0201-binding peptide epitope-specific T-cell responses were found after vaccination of HLA-A*0201-transgenic and non-transgenic mice with MVA-DeltaIL1betaR.
2991 15961574 To identify DCs with differing abilities to direct Th1/Th2 cell differentiation, we cultured mouse bone marrow progenitors in granulocyte macrophage-colony stimulating factor (GM), GM + interleukin (IL)-4, or GM + IL-15 and generated three distinct DC populations.
2992 15961574 The GM + IL-4 DCs expressed high levels of CD80/CD86 and major histocompatibility complex (MHC) class II and produced low levels of IL-12p70.
2993 15961574 GM and GM + IL-15 DCs expressed low levels of CD80/CD86 and MHC class II.
2994 15961574 The GM + IL-15 DCs produced high levels of IL-12p70 and interferon (IFN)-gamma, whereas GM DCs produced only high levels of IL-12p70.
2995 15961574 Naive T cells stimulated with GM + IL-4 DCs secreted high levels of IL-4 and IL-5 in addition to IFN-gamma.
2996 15961574 In contrast, the GM + IL-15 DCs induced higher IFN-gamma production by T cells with little or no Th2 cytokines.
2997 15961574 To identify DCs with differing abilities to direct Th1/Th2 cell differentiation, we cultured mouse bone marrow progenitors in granulocyte macrophage-colony stimulating factor (GM), GM + interleukin (IL)-4, or GM + IL-15 and generated three distinct DC populations.
2998 15961574 The GM + IL-4 DCs expressed high levels of CD80/CD86 and major histocompatibility complex (MHC) class II and produced low levels of IL-12p70.
2999 15961574 GM and GM + IL-15 DCs expressed low levels of CD80/CD86 and MHC class II.
3000 15961574 The GM + IL-15 DCs produced high levels of IL-12p70 and interferon (IFN)-gamma, whereas GM DCs produced only high levels of IL-12p70.
3001 15961574 Naive T cells stimulated with GM + IL-4 DCs secreted high levels of IL-4 and IL-5 in addition to IFN-gamma.
3002 15961574 In contrast, the GM + IL-15 DCs induced higher IFN-gamma production by T cells with little or no Th2 cytokines.
3003 15972497 Our results showed that StxB1 and mStx1, but not native Stx1 (nStx1), resulted in enhanced expression of CD86, CD40, and major histocompatibility complex (MHC) class II molecules and, to some extent, also enhanced the expression of CD80 on bone marrow-derived DCs.
3004 15972497 StxB1-treated DCs exhibited an increase in tumor necrosis factor alpha and interleukin-12 (IL-12) production, a stimulation of DO11.10 T-cell proliferation, and the production of both Th1 and Th2 cytokines, including gamma interferon (IFN-gamma), IL-4, IL-5, IL-6, and IL-10.
3005 15972497 When mice were given StxB1 subcutaneously, the levels of CD80, CD86, and CD40, as well as MHC class II expression by splenic DCs, were enhanced.
3006 15972497 OVA-specific CD4+ T cells isolated from mice immunized with OVA plus mStx1 or StxB1 produced IFN-gamma, IL-4, IL-5, IL-6, and IL-10, indicating that mStx1 and StxB1 elicit both Th1- and Th2-type responses.
3007 15972497 Our results showed that StxB1 and mStx1, but not native Stx1 (nStx1), resulted in enhanced expression of CD86, CD40, and major histocompatibility complex (MHC) class II molecules and, to some extent, also enhanced the expression of CD80 on bone marrow-derived DCs.
3008 15972497 StxB1-treated DCs exhibited an increase in tumor necrosis factor alpha and interleukin-12 (IL-12) production, a stimulation of DO11.10 T-cell proliferation, and the production of both Th1 and Th2 cytokines, including gamma interferon (IFN-gamma), IL-4, IL-5, IL-6, and IL-10.
3009 15972497 When mice were given StxB1 subcutaneously, the levels of CD80, CD86, and CD40, as well as MHC class II expression by splenic DCs, were enhanced.
3010 15972497 OVA-specific CD4+ T cells isolated from mice immunized with OVA plus mStx1 or StxB1 produced IFN-gamma, IL-4, IL-5, IL-6, and IL-10, indicating that mStx1 and StxB1 elicit both Th1- and Th2-type responses.
3011 15980443 Specifically, we offer the possibility of identifying promiscuous peptide binders to five distinct HLA class I supertypes (A2, A3, B7, A24 and B15).
3012 15981208 In cellular activation, the CD28 ligands B7-1 (CD80) and B7-2 (CD86) are thought to play nearly identical roles in T cell activation.
3013 15981208 We monitored the T cell response upon co-culture with HLA Class I-matched and mismatched renal carcinoma cells, respectively, that express different levels of B7-1 and B7-2, respectively.
3014 15981208 In a HLA Class I-mismatched co-culture, T cell proliferation, IFN-gamma and GM-CSF secretion equally depend on the levels of B7-1 and B7-2 on tumor cells.
3015 15981208 In contrast, in a HLA Class I-matched situation, B7-2 is more effective in the induction of IFN-gamma and GM-CSF secretion than B7-1, but both B7 molecules induce T cell proliferation equally efficient.
3016 15981208 B7-2 is more effective than B7-1 in inducing TNF-alpha and IL-10 secretion in both HLA Class I-matched and mismatched situations.
3017 15981208 The distinct patterns of cytokine induction by B7-1 and B7-2 obviously depend on the HLA Class I compatibility.
3018 15981208 In cellular activation, the CD28 ligands B7-1 (CD80) and B7-2 (CD86) are thought to play nearly identical roles in T cell activation.
3019 15981208 We monitored the T cell response upon co-culture with HLA Class I-matched and mismatched renal carcinoma cells, respectively, that express different levels of B7-1 and B7-2, respectively.
3020 15981208 In a HLA Class I-mismatched co-culture, T cell proliferation, IFN-gamma and GM-CSF secretion equally depend on the levels of B7-1 and B7-2 on tumor cells.
3021 15981208 In contrast, in a HLA Class I-matched situation, B7-2 is more effective in the induction of IFN-gamma and GM-CSF secretion than B7-1, but both B7 molecules induce T cell proliferation equally efficient.
3022 15981208 B7-2 is more effective than B7-1 in inducing TNF-alpha and IL-10 secretion in both HLA Class I-matched and mismatched situations.
3023 15981208 The distinct patterns of cytokine induction by B7-1 and B7-2 obviously depend on the HLA Class I compatibility.
3024 15981208 In cellular activation, the CD28 ligands B7-1 (CD80) and B7-2 (CD86) are thought to play nearly identical roles in T cell activation.
3025 15981208 We monitored the T cell response upon co-culture with HLA Class I-matched and mismatched renal carcinoma cells, respectively, that express different levels of B7-1 and B7-2, respectively.
3026 15981208 In a HLA Class I-mismatched co-culture, T cell proliferation, IFN-gamma and GM-CSF secretion equally depend on the levels of B7-1 and B7-2 on tumor cells.
3027 15981208 In contrast, in a HLA Class I-matched situation, B7-2 is more effective in the induction of IFN-gamma and GM-CSF secretion than B7-1, but both B7 molecules induce T cell proliferation equally efficient.
3028 15981208 B7-2 is more effective than B7-1 in inducing TNF-alpha and IL-10 secretion in both HLA Class I-matched and mismatched situations.
3029 15981208 The distinct patterns of cytokine induction by B7-1 and B7-2 obviously depend on the HLA Class I compatibility.
3030 15981208 In cellular activation, the CD28 ligands B7-1 (CD80) and B7-2 (CD86) are thought to play nearly identical roles in T cell activation.
3031 15981208 We monitored the T cell response upon co-culture with HLA Class I-matched and mismatched renal carcinoma cells, respectively, that express different levels of B7-1 and B7-2, respectively.
3032 15981208 In a HLA Class I-mismatched co-culture, T cell proliferation, IFN-gamma and GM-CSF secretion equally depend on the levels of B7-1 and B7-2 on tumor cells.
3033 15981208 In contrast, in a HLA Class I-matched situation, B7-2 is more effective in the induction of IFN-gamma and GM-CSF secretion than B7-1, but both B7 molecules induce T cell proliferation equally efficient.
3034 15981208 B7-2 is more effective than B7-1 in inducing TNF-alpha and IL-10 secretion in both HLA Class I-matched and mismatched situations.
3035 15981208 The distinct patterns of cytokine induction by B7-1 and B7-2 obviously depend on the HLA Class I compatibility.
3036 15981208 In cellular activation, the CD28 ligands B7-1 (CD80) and B7-2 (CD86) are thought to play nearly identical roles in T cell activation.
3037 15981208 We monitored the T cell response upon co-culture with HLA Class I-matched and mismatched renal carcinoma cells, respectively, that express different levels of B7-1 and B7-2, respectively.
3038 15981208 In a HLA Class I-mismatched co-culture, T cell proliferation, IFN-gamma and GM-CSF secretion equally depend on the levels of B7-1 and B7-2 on tumor cells.
3039 15981208 In contrast, in a HLA Class I-matched situation, B7-2 is more effective in the induction of IFN-gamma and GM-CSF secretion than B7-1, but both B7 molecules induce T cell proliferation equally efficient.
3040 15981208 B7-2 is more effective than B7-1 in inducing TNF-alpha and IL-10 secretion in both HLA Class I-matched and mismatched situations.
3041 15981208 The distinct patterns of cytokine induction by B7-1 and B7-2 obviously depend on the HLA Class I compatibility.
3042 15989466 The most frequently represented HLA-A and -B alleles were HLA-A11, A02, and A33 expressed by 35.7, 23.2, and 21.4% of the patients, respectively, and HLA-B75, B46, and B62 expressed by 35.7, 25, and 17.9% of the patients, respectively.
3043 15993518 We demonstrate that a recombinant MVSchw virus expressing an HIV-1-derived CTL polyepitope primes effective HLA-A0201-restricted CTLs against multiple conserved HIV-1 epitopes in mice susceptible to measles and humanized for the major histocompatibility complex (MHC) class-I molecule HLA-A0201.
3044 16011514 Antitumour activity mediated by CD4+ cytotoxic T lymphocytes against MHC class II-negative mouse hepatocellular carcinoma induced by dendritic cell vaccine and interleukin-12.
3045 16011514 Antitumour activity induced by DC/BNL + IL-12 was abrogated by depletion of CD4+ T cells, but not by depletion of CD8+ T cells or natural killer cells.
3046 16011514 Splenic CD4+ T cells and CD8+ T cells from DC/BNL-treated mice showed cytotoxic activity against BNL cells after 3 days of incubation with DC/BNL, although BNL cells do not express major histocompatibility complex (MHC) class II molecules even after treatment with interferon (INF)-gamma.
3047 16011514 Immunofluorescence microscopy demonstrated that abundant CD4+ T cells and MHC class II-positive macrophages, but not CD8(+) T cells, had infiltrated tumour tissue in mice treated with DC/BNL + IL-12.
3048 16011514 Flow cytometric analysis of tumour-infiltrating cells in mice treated with DC/BNL + IL-12 showed increases in CD4+ T cells and MHC class II+ CD11b+ cells but not in CD8+ T cells or MHC class I+ CD11b+ cells.
3049 16011514 Our results suggest that, in BNL-bearing mice treated with DC/BNL + IL-12, tumour macrophages activated by INF-gamma produced by IL-12-stimulated T cells might present BNL tumour antigens and activate DC/BNL-primed CD4+ cytotoxic T lymphocytes (CTLs) in a MHC class II-dependent manner, leading to perforin-mediated bystander killing of neighbouring MHC class II-negative tumour cells.
3050 16011514 Antitumour activity mediated by CD4+ cytotoxic T lymphocytes against MHC class II-negative mouse hepatocellular carcinoma induced by dendritic cell vaccine and interleukin-12.
3051 16011514 Antitumour activity induced by DC/BNL + IL-12 was abrogated by depletion of CD4+ T cells, but not by depletion of CD8+ T cells or natural killer cells.
3052 16011514 Splenic CD4+ T cells and CD8+ T cells from DC/BNL-treated mice showed cytotoxic activity against BNL cells after 3 days of incubation with DC/BNL, although BNL cells do not express major histocompatibility complex (MHC) class II molecules even after treatment with interferon (INF)-gamma.
3053 16011514 Immunofluorescence microscopy demonstrated that abundant CD4+ T cells and MHC class II-positive macrophages, but not CD8(+) T cells, had infiltrated tumour tissue in mice treated with DC/BNL + IL-12.
3054 16011514 Flow cytometric analysis of tumour-infiltrating cells in mice treated with DC/BNL + IL-12 showed increases in CD4+ T cells and MHC class II+ CD11b+ cells but not in CD8+ T cells or MHC class I+ CD11b+ cells.
3055 16011514 Our results suggest that, in BNL-bearing mice treated with DC/BNL + IL-12, tumour macrophages activated by INF-gamma produced by IL-12-stimulated T cells might present BNL tumour antigens and activate DC/BNL-primed CD4+ cytotoxic T lymphocytes (CTLs) in a MHC class II-dependent manner, leading to perforin-mediated bystander killing of neighbouring MHC class II-negative tumour cells.
3056 16011514 Antitumour activity mediated by CD4+ cytotoxic T lymphocytes against MHC class II-negative mouse hepatocellular carcinoma induced by dendritic cell vaccine and interleukin-12.
3057 16011514 Antitumour activity induced by DC/BNL + IL-12 was abrogated by depletion of CD4+ T cells, but not by depletion of CD8+ T cells or natural killer cells.
3058 16011514 Splenic CD4+ T cells and CD8+ T cells from DC/BNL-treated mice showed cytotoxic activity against BNL cells after 3 days of incubation with DC/BNL, although BNL cells do not express major histocompatibility complex (MHC) class II molecules even after treatment with interferon (INF)-gamma.
3059 16011514 Immunofluorescence microscopy demonstrated that abundant CD4+ T cells and MHC class II-positive macrophages, but not CD8(+) T cells, had infiltrated tumour tissue in mice treated with DC/BNL + IL-12.
3060 16011514 Flow cytometric analysis of tumour-infiltrating cells in mice treated with DC/BNL + IL-12 showed increases in CD4+ T cells and MHC class II+ CD11b+ cells but not in CD8+ T cells or MHC class I+ CD11b+ cells.
3061 16011514 Our results suggest that, in BNL-bearing mice treated with DC/BNL + IL-12, tumour macrophages activated by INF-gamma produced by IL-12-stimulated T cells might present BNL tumour antigens and activate DC/BNL-primed CD4+ cytotoxic T lymphocytes (CTLs) in a MHC class II-dependent manner, leading to perforin-mediated bystander killing of neighbouring MHC class II-negative tumour cells.
3062 16011514 Antitumour activity mediated by CD4+ cytotoxic T lymphocytes against MHC class II-negative mouse hepatocellular carcinoma induced by dendritic cell vaccine and interleukin-12.
3063 16011514 Antitumour activity induced by DC/BNL + IL-12 was abrogated by depletion of CD4+ T cells, but not by depletion of CD8+ T cells or natural killer cells.
3064 16011514 Splenic CD4+ T cells and CD8+ T cells from DC/BNL-treated mice showed cytotoxic activity against BNL cells after 3 days of incubation with DC/BNL, although BNL cells do not express major histocompatibility complex (MHC) class II molecules even after treatment with interferon (INF)-gamma.
3065 16011514 Immunofluorescence microscopy demonstrated that abundant CD4+ T cells and MHC class II-positive macrophages, but not CD8(+) T cells, had infiltrated tumour tissue in mice treated with DC/BNL + IL-12.
3066 16011514 Flow cytometric analysis of tumour-infiltrating cells in mice treated with DC/BNL + IL-12 showed increases in CD4+ T cells and MHC class II+ CD11b+ cells but not in CD8+ T cells or MHC class I+ CD11b+ cells.
3067 16011514 Our results suggest that, in BNL-bearing mice treated with DC/BNL + IL-12, tumour macrophages activated by INF-gamma produced by IL-12-stimulated T cells might present BNL tumour antigens and activate DC/BNL-primed CD4+ cytotoxic T lymphocytes (CTLs) in a MHC class II-dependent manner, leading to perforin-mediated bystander killing of neighbouring MHC class II-negative tumour cells.
3068 16011514 Antitumour activity mediated by CD4+ cytotoxic T lymphocytes against MHC class II-negative mouse hepatocellular carcinoma induced by dendritic cell vaccine and interleukin-12.
3069 16011514 Antitumour activity induced by DC/BNL + IL-12 was abrogated by depletion of CD4+ T cells, but not by depletion of CD8+ T cells or natural killer cells.
3070 16011514 Splenic CD4+ T cells and CD8+ T cells from DC/BNL-treated mice showed cytotoxic activity against BNL cells after 3 days of incubation with DC/BNL, although BNL cells do not express major histocompatibility complex (MHC) class II molecules even after treatment with interferon (INF)-gamma.
3071 16011514 Immunofluorescence microscopy demonstrated that abundant CD4+ T cells and MHC class II-positive macrophages, but not CD8(+) T cells, had infiltrated tumour tissue in mice treated with DC/BNL + IL-12.
3072 16011514 Flow cytometric analysis of tumour-infiltrating cells in mice treated with DC/BNL + IL-12 showed increases in CD4+ T cells and MHC class II+ CD11b+ cells but not in CD8+ T cells or MHC class I+ CD11b+ cells.
3073 16011514 Our results suggest that, in BNL-bearing mice treated with DC/BNL + IL-12, tumour macrophages activated by INF-gamma produced by IL-12-stimulated T cells might present BNL tumour antigens and activate DC/BNL-primed CD4+ cytotoxic T lymphocytes (CTLs) in a MHC class II-dependent manner, leading to perforin-mediated bystander killing of neighbouring MHC class II-negative tumour cells.
3074 16044253 Splenocytes obtained from 3H1-CpG-immunized mice showed an increased proliferative CD4(+) Th1-type T-cell response when stimulated in vitro with 3H1 or CEA and secreted elevated levels of Th1 cytokines (IL-2, IFN-gamma).
3075 16044253 This vaccine also induced MHC class I antigen-restricted CD8(+) T-cell responses.
3076 16061684 CD4+ T cells are able to promote tumor growth through inhibition of tumor-specific CD8+ T-cell responses in tumor-bearing hosts.
3077 16061684 We analyzed the contribution of the CD4+ T-cell population to the induction or suppression of tumor-specific CD8+ T cells in a tumor model in which eradication of tumors crucially depends on CD8+ T cell-mediated immunity.
3078 16061684 Vaccine-mediated induction of protective antitumor immunity in the preventive setting (i.e., before tumor challenge) was CD4+ T cell dependent because depletion of this T-cell subset prevented CD8+ T-cell induction.
3079 16061684 In contrast, depletion of CD4+ cells in mice bearing established E1A+ tumors empowered the mice to raise strong CD8+ T-cell immunity capable of tumor eradication without the need for tumor-specific vaccination.
3080 16061684 Spontaneous eradication of tumors, which had initially grown out, was similarly observed in MHC class II-deficient mice, supporting the notion that the tumor-bearing mice harbor a class II MHC-restricted CD4+ T-cell subset capable of suppressing a tumor-specific CD8+ T-cell immune response.
3081 16061684 The deleterious effects of the presence of CD4+ T cells in tumor-bearing hosts could be overcome by CD40-triggering or injection of CpG.
3082 16078831 Our results also indicate that MDP-C is an effective stimulator for production of interleukin-2 and interleukin-12 by murine bone marrow derived dendritic cells (BMDCs) and production of interferon-gamma by CTLs.
3083 16078831 Additionally, MDP-C increases the expression levels of several surface molecules, including CD11c, MHC class I, and intercellular adhesion molecule-1 in BMDCs.
3084 16098640 Here, we report time-course changes in expression levels, assessed by real-time RT-PCR of IL-1 beta, Mx, two beta-2-microglobulin variants and MHC class II beta, from 2 to 19 days post vaccination with a multi-component oil-adjuvanted vaccine.
3085 16107020 Immunofluorescense method was used to determine the expression of T- and B-lymphocyte markers, antigens of major histocompatibility complex (MHC) class I and II, and CD86 co-stimulating molecule in the cell lines.
3086 16108831 These peptides showed IGSF11-specific cytotoxic activity in an HLA-A*0201-restricted fashion, suggesting that these peptides may be applicable for cancer immunotherapy.
3087 16113607 Twenty-two HLA A*0201 patients with stage IV melanoma were enrolled in a phase 1 safety and feasibility trial using a composite dendritic cell (DC) vaccine generated by culturing CD34 hematopoietic progenitors and activated with IFN-alpha.
3088 16113607 The DC vaccine was loaded with peptides derived from four melanoma tissue differentiation antigens (MART-1, tyrosinase, MAGE-3, and gp100) and influenza matrix peptide (Flu-MP).
3089 16113607 Melanoma-peptide-specific recall memory CD8 T cells able to secrete IFN-gamma and to proliferate could be detected in six of the seven analyzed patients.
3090 16116238 Viral vectors may address both of these issues, as they can be used to deliver intact tumor Ags to DCs, and have been shown to inhibit the suppression mediated by CD4+CD25+ regulatory T cells.
3091 16116238 VRP infection of immature DCs was superior to TNF-alpha treatment at inducing phenotypic maturation of DCs, and was comparable to LPS stimulation.
3092 16116238 Additionally, VRP-infected DC cultures secreted substantial amounts of the proinflammatory cytokines IL-6, TNF-alpha, and IFN-alpha.
3093 16116238 Finally, DCs transduced with a VRP encoding the influenza matrix protein (FMP) stimulated 50% greater expansion of FMP-specific CD8+ CTL when compared with TNF-alpha-matured DCs pulsed with an HLA-A*0201-restricted FMP peptide.
3094 16126320 Their HLA-DRbeta1* molecule binding ability was also determined to ascertain association between their 3D structure and ability to bind to Major Histocompatibility Complex Class-II molecules (MHC-II). 1H Nuclear Magnetic Resonance analysis and structure calculations clearly showed that these modified HABPs inducing protective cellular immune responses (but not producing antibodies against malaria) adopted special structural configuration to fit into the MHC II-peptide-TCR complex.
3095 16154304 In this study, we investigated the effect of babassu mesocarp flour aqueous extract (BM) on C3H/HePas mice peritoneal cellular migration and macrophage activation by measuring the nitric oxide (NO), hydrogen peroxide (H(2)O(2)) and tumor necrosis factor (TNF) release, spreading activity and major histocompatibility complex (MHC) class II expression.
3096 16154304 Our results demonstrate that BM injected once ip in mice at 10 and 20 mg/kg increased the cellular influx to the peritoneal cavity, the MHC class II expression and the spreading ability, and also induced the production of NO, TNF and H(2)O(2).
3097 16154304 In this study, we investigated the effect of babassu mesocarp flour aqueous extract (BM) on C3H/HePas mice peritoneal cellular migration and macrophage activation by measuring the nitric oxide (NO), hydrogen peroxide (H(2)O(2)) and tumor necrosis factor (TNF) release, spreading activity and major histocompatibility complex (MHC) class II expression.
3098 16154304 Our results demonstrate that BM injected once ip in mice at 10 and 20 mg/kg increased the cellular influx to the peritoneal cavity, the MHC class II expression and the spreading ability, and also induced the production of NO, TNF and H(2)O(2).
3099 16176847 DNA- and modified virus Ankara (MVA)-vectored candidate vaccines expressing human immunodeficiency virus type 1 (HIV-1) clade A-derived p24/p17 gag fused to a string of HLA class I epitopes, called HIVA, were tested in phase I trials in healthy, HIV-1/2-uninfected adults in Oxford, United Kingdom.
3100 16181335 However, in some circumstances, antigens from the extracellular environment can be presented on MHC class I molecules and stimulate CD8(+) T-cell immunity, a process termed cross-presentation.
3101 16181335 In one pathway, the antigen is transferred from the phagosome into the cytosol, where it is hydrolyzed by proteasomes into oligopeptides that are then transported by the transporter associated with antigen processing to MHC class I molecules in the endoplasmic reticulum or phagosomes.
3102 16181335 In addition to the critical role of cross-presentation in normal immune physiology, this pathway has considerable potential for being exploited for developing subunit vaccines that elicit both CD4(+) and CD8(+) T-cell immunity.
3103 16181335 However, in some circumstances, antigens from the extracellular environment can be presented on MHC class I molecules and stimulate CD8(+) T-cell immunity, a process termed cross-presentation.
3104 16181335 In one pathway, the antigen is transferred from the phagosome into the cytosol, where it is hydrolyzed by proteasomes into oligopeptides that are then transported by the transporter associated with antigen processing to MHC class I molecules in the endoplasmic reticulum or phagosomes.
3105 16181335 In addition to the critical role of cross-presentation in normal immune physiology, this pathway has considerable potential for being exploited for developing subunit vaccines that elicit both CD4(+) and CD8(+) T-cell immunity.
3106 16185791 Using microarray analysis, humoral defense-related genes such as complement component C3, complement regulatory plasma proteins, IgM, IgD, MHC class II-associated invariant chain and CD20 receptor were observed to be up-regulated by the VHSg recombinant protein vaccine at 1 or 21 days post vaccination.
3107 16204084 Our results show that vaccination with the PE(DeltaIII)-E7-KDEL3 fusion protein enhances MHC class I and II presentation of E7, leading to dramatic increases in the number of E7-specific CD8+ and CD4+ T-cell precursors and markedly raised titers of E7-specific antibodies.
3108 16207252 A novel CD4-CD8alpha+CD205+CD11b- murine spleen dendritic cell line: establishment, characterization and functional analysis in a model of vaccination to toxoplasmosis.
3109 16207252 These cells display similar morphology, phenotype and activity to CD4(-)CD8alpha(+)CD205(+)CD11b(-) DCs purified ex vivo.
3110 16207252 Toxoplasma gondii antigen was shown to be taken up by these cells and to increase class I and class II major histocompatibility complex (MHC), CD40, CD80 and CD86 surface expression.
3111 16207252 The SRDC or CD4(-)CD8alpha(+)CD205(+)CD11b(-) DC line can be expected to be a very useful tool for immunobiology studies of DC.
3112 16210659 HLA-A*0201, HLA-A*1101, and HLA-B*0702 transgenic mice recognize numerous poxvirus determinants from a wide variety of viral gene products.
3113 16210659 Using this panel in conjunction with CTLs from vaccinia virus-infected HLA transgenic mice, we identified 14 HLA-A*0201-, 4 HLA-A*1101-, and 3 HLA-B*0702-restricted CD8(+) T cell determinants distributed over 20 distinct proteins.
3114 16210659 HLA-A*0201, HLA-A*1101, and HLA-B*0702 transgenic mice recognize numerous poxvirus determinants from a wide variety of viral gene products.
3115 16210659 Using this panel in conjunction with CTLs from vaccinia virus-infected HLA transgenic mice, we identified 14 HLA-A*0201-, 4 HLA-A*1101-, and 3 HLA-B*0702-restricted CD8(+) T cell determinants distributed over 20 distinct proteins.
3116 16220325 Since WT1 encodes MHC class I-restricted peptides recognized by cytotoxic T lymphocytes (CTL), WT1 has been considered as a promising tumor-associated antigen (TAA) for developing anticancer immunotherapy.
3117 16220325 Interestingly, the two WT1 HTL epitopes described here are closely situated to known MHC class I-restricted CTL epitopes, raising the possibility of stimulating CTL and HTL responses using a relatively small synthetic peptide vaccine.
3118 16227247 An additional 18% of amino acid mutations represented substitutions toward common clade B consensus sequence residues, nine of which were strongly associated with HLA class I alleles not expressed by the subjects and thus indicative of reversions of transmitted CD8 escape mutations.
3119 16227284 The results indicate that (i) the rodent core proteins are equal in immunogenicity to or more immunogenic than HBcAg at the B-cell and T-cell levels; (ii) major histocompatibility complex (MHC) genes influence the immune response to the rodent core proteins (however, nonresponder haplotypes were not identified); (iii) WHcAg can behave as a T-cell-independent antigen in athymic mice; (iv) the rodent core proteins are not significantly cross-reactive with the HBcAg at the antibody level (however, the nonparticulate "eAgs" do appear to be cross-reactive); (v) the rodent core proteins are only partially cross-reactive with HBcAg at the CD4+ T-cell level, depending on MHC haplotype; and (vi) the rodent core proteins are competent to function as vaccine carrier platforms for heterologous, B-cell epitopes.
3120 16243831 More efficient induction of HLA-A*0201-restricted and carcinoembryonic antigen (CEA)-specific CTL response by immunization with exosomes prepared from heat-stressed CEA-positive tumor cells.
3121 16267030 Tetramer analysis indicated superior generation of HLA-A2.1, CD8+ T lymphocytes specific for NY-ESO-1(157-165) with PTD-NY-ESO-1 compared with NY-ESO-1 control protein (44% versus 2%, respectively).
3122 16267030 NY-ESO-1-specific T lymphocytes generated with PTD-NY-ESO-1 secreted IFN-gamma indicative of a Tc1-type cytokine response.
3123 16267030 Thus, PTD-NY-ESO-1 accesses the cytoplasm by protein transduction, is processed by the proteasome, and NY-ESO-1 peptides presented by HLA class I elicit NY-ESO-1-specific T lymphocytes.
3124 16267033 A novel strategy for the discovery of MHC class II-restricted tumor antigens: identification of a melanotransferrin helper T-cell epitope.
3125 16267033 The limited availability of MHC class II-associated tumor antigens is still viewed as a major obstacle in the use of CD4+ T cells in cancer vaccines.
3126 16267033 A novel strategy for the discovery of MHC class II-restricted tumor antigens: identification of a melanotransferrin helper T-cell epitope.
3127 16267033 The limited availability of MHC class II-associated tumor antigens is still viewed as a major obstacle in the use of CD4+ T cells in cancer vaccines.
3128 16272285 HLA class I tetramers have revolutionized the study of Ag-specific CD8+ T cell responses.
3129 16272285 We find rapid and efficient staining of DR1- and DR4-restricted CD4+ cell lines and clones and show that TCR internalization is not a requirement for immunological staining.
3130 16279537 The generation of ripe dendrite cells (DC) of marrow origin was obtained with the use of the vaccine Immunovac-BN-4, an immunomodulator of microbial origin, as well as Klebsiella pneumoniae LPS and TNF-alpha, as ripening inducers.
3131 16279537 The immunophenotype of cells altered from CD34+, CD38-, CD40-, CD80-, CD86-, MHC I-, MHC II-, F4/80- to CD34-, CD38+, CD40+, CD80+, MHC I+, MHC II+, F4/ 80(low).
3132 16279537 In culture medium with ripe DC the levels of such cytokines as IL-1b, IL-6, IL-12, IFN-gamma, TNF-alpha significantly increased and the production of IL-4 decreased.
3133 16279537 The content of IL-2 and IL-10 remained unchanged.
3134 16281981 Lysis of autologous melanoma cells was not blocked by anti-HLA class I or class II antibodies, confirming that the cytolytic activity of the CD8+ CTL was HLA-unrestricted.
3135 16300869 Here, we investigated the possibility to enhance the CD8 response against the human and mouse shared TERT(572Y) HLA-A*0201 restricted modified cryptic peptide by using ODN-CpG as adjuvant.
3136 16300869 Those cells and especially the CD11c+ CD11b- CD8a+ lymphoid and the CD11c+ B220+ plasmacytoid dendritic cells were activated as shown by up-regulation of CD40 at their cell surface.
3137 16315876 These fusion cells expressed major histocompatibility complex (MHC) class I and MHC class II, CD86, CD11c and CD8alpha.
3138 16328003 Moderately immunogenic HPV 16-associated murine tumour cell line mimicking human HPV 16-associated neoplasms TC-1 (MHC class I(+)) and its variants, TC-1/P3C10 and TC-1/A9, with a marked down-regulation of MHC I molecules, were used to examine the effect of local interleukin 12 (IL-12) gene therapy for the treatment of early tumour transplants and minimal residual tumour disease obtained after cytoreductive chemotherapy (CMRTD).
3139 16328003 It was found that peritumoral administration of IL-12-producing tumour cell vaccines (single dose, day 8 after tumour cell administration) inhibited the growth of both TC-1 (MHC class I positive) tumours and their MHC class I-deficient variants.
3140 16328003 This treatment was followed by peritumoral s.c. administration of genetically modified TC-1 (MHC class I positive) or MK16/I/IIIABC (MHC class I negative) vaccines producing IL-12 (single dose, day 7 after chemotherapy) or with recombinant interleukin 12 (rIL-12) in two cycles of 5 daily doses (days 8-19) after chemotherapy.
3141 16328003 This combined therapy significantly inhibited the growth of TC-1 and TC-1/A9 (MHC class I-) tumours.
3142 16328003 When the combined therapy of TC-1 (MHC class I positive) tumours was followed by peritumoral administration of bone marrow dendritic cell (BMDC) vaccines, the IL-12-mediated inhibitory effect was significantly boosted.
3143 16328003 Moderately immunogenic HPV 16-associated murine tumour cell line mimicking human HPV 16-associated neoplasms TC-1 (MHC class I(+)) and its variants, TC-1/P3C10 and TC-1/A9, with a marked down-regulation of MHC I molecules, were used to examine the effect of local interleukin 12 (IL-12) gene therapy for the treatment of early tumour transplants and minimal residual tumour disease obtained after cytoreductive chemotherapy (CMRTD).
3144 16328003 It was found that peritumoral administration of IL-12-producing tumour cell vaccines (single dose, day 8 after tumour cell administration) inhibited the growth of both TC-1 (MHC class I positive) tumours and their MHC class I-deficient variants.
3145 16328003 This treatment was followed by peritumoral s.c. administration of genetically modified TC-1 (MHC class I positive) or MK16/I/IIIABC (MHC class I negative) vaccines producing IL-12 (single dose, day 7 after chemotherapy) or with recombinant interleukin 12 (rIL-12) in two cycles of 5 daily doses (days 8-19) after chemotherapy.
3146 16328003 This combined therapy significantly inhibited the growth of TC-1 and TC-1/A9 (MHC class I-) tumours.
3147 16328003 When the combined therapy of TC-1 (MHC class I positive) tumours was followed by peritumoral administration of bone marrow dendritic cell (BMDC) vaccines, the IL-12-mediated inhibitory effect was significantly boosted.
3148 16328003 Moderately immunogenic HPV 16-associated murine tumour cell line mimicking human HPV 16-associated neoplasms TC-1 (MHC class I(+)) and its variants, TC-1/P3C10 and TC-1/A9, with a marked down-regulation of MHC I molecules, were used to examine the effect of local interleukin 12 (IL-12) gene therapy for the treatment of early tumour transplants and minimal residual tumour disease obtained after cytoreductive chemotherapy (CMRTD).
3149 16328003 It was found that peritumoral administration of IL-12-producing tumour cell vaccines (single dose, day 8 after tumour cell administration) inhibited the growth of both TC-1 (MHC class I positive) tumours and their MHC class I-deficient variants.
3150 16328003 This treatment was followed by peritumoral s.c. administration of genetically modified TC-1 (MHC class I positive) or MK16/I/IIIABC (MHC class I negative) vaccines producing IL-12 (single dose, day 7 after chemotherapy) or with recombinant interleukin 12 (rIL-12) in two cycles of 5 daily doses (days 8-19) after chemotherapy.
3151 16328003 This combined therapy significantly inhibited the growth of TC-1 and TC-1/A9 (MHC class I-) tumours.
3152 16328003 When the combined therapy of TC-1 (MHC class I positive) tumours was followed by peritumoral administration of bone marrow dendritic cell (BMDC) vaccines, the IL-12-mediated inhibitory effect was significantly boosted.
3153 16328003 Moderately immunogenic HPV 16-associated murine tumour cell line mimicking human HPV 16-associated neoplasms TC-1 (MHC class I(+)) and its variants, TC-1/P3C10 and TC-1/A9, with a marked down-regulation of MHC I molecules, were used to examine the effect of local interleukin 12 (IL-12) gene therapy for the treatment of early tumour transplants and minimal residual tumour disease obtained after cytoreductive chemotherapy (CMRTD).
3154 16328003 It was found that peritumoral administration of IL-12-producing tumour cell vaccines (single dose, day 8 after tumour cell administration) inhibited the growth of both TC-1 (MHC class I positive) tumours and their MHC class I-deficient variants.
3155 16328003 This treatment was followed by peritumoral s.c. administration of genetically modified TC-1 (MHC class I positive) or MK16/I/IIIABC (MHC class I negative) vaccines producing IL-12 (single dose, day 7 after chemotherapy) or with recombinant interleukin 12 (rIL-12) in two cycles of 5 daily doses (days 8-19) after chemotherapy.
3156 16328003 This combined therapy significantly inhibited the growth of TC-1 and TC-1/A9 (MHC class I-) tumours.
3157 16328003 When the combined therapy of TC-1 (MHC class I positive) tumours was followed by peritumoral administration of bone marrow dendritic cell (BMDC) vaccines, the IL-12-mediated inhibitory effect was significantly boosted.
3158 16328003 Moderately immunogenic HPV 16-associated murine tumour cell line mimicking human HPV 16-associated neoplasms TC-1 (MHC class I(+)) and its variants, TC-1/P3C10 and TC-1/A9, with a marked down-regulation of MHC I molecules, were used to examine the effect of local interleukin 12 (IL-12) gene therapy for the treatment of early tumour transplants and minimal residual tumour disease obtained after cytoreductive chemotherapy (CMRTD).
3159 16328003 It was found that peritumoral administration of IL-12-producing tumour cell vaccines (single dose, day 8 after tumour cell administration) inhibited the growth of both TC-1 (MHC class I positive) tumours and their MHC class I-deficient variants.
3160 16328003 This treatment was followed by peritumoral s.c. administration of genetically modified TC-1 (MHC class I positive) or MK16/I/IIIABC (MHC class I negative) vaccines producing IL-12 (single dose, day 7 after chemotherapy) or with recombinant interleukin 12 (rIL-12) in two cycles of 5 daily doses (days 8-19) after chemotherapy.
3161 16328003 This combined therapy significantly inhibited the growth of TC-1 and TC-1/A9 (MHC class I-) tumours.
3162 16328003 When the combined therapy of TC-1 (MHC class I positive) tumours was followed by peritumoral administration of bone marrow dendritic cell (BMDC) vaccines, the IL-12-mediated inhibitory effect was significantly boosted.
3163 16331510 Immunologic significance of HLA class I genes in measles virus-specific IFN-gamma and IL-4 cytokine immune responses.
3164 16331510 Median values for measles-specific interferon gamma (IFN-gamma) and interleukin-4 (IL-4) cytokines were 40.7 pg/ml [interquartile range (IQR) 8.1-176.7] and 9.7 pg/ml (IQR 2.8-24.3), respectively.
3165 16331510 Class I HLA-A (*0101 and *3101) and HLA-Cw (*0303 and *0501) alleles were significantly associated with measles-virus-induced IFN-gamma secretion.
3166 16331510 HLA-A*3101 and Cw*0303 were associated with a higher median IFN-gamma response, while A*0101 and Cw*0501 were associated with lower measles-specific IFN-gamma response.
3167 16331510 We found limited associations between HLA class I gene polymorphisms and Th2-like (IL-4) immune responses after measles vaccination, indicating that HLA class I molecules may have a limited effect on measles-vaccine-induced IL-4 secretion.
3168 16331510 Immunologic significance of HLA class I genes in measles virus-specific IFN-gamma and IL-4 cytokine immune responses.
3169 16331510 Median values for measles-specific interferon gamma (IFN-gamma) and interleukin-4 (IL-4) cytokines were 40.7 pg/ml [interquartile range (IQR) 8.1-176.7] and 9.7 pg/ml (IQR 2.8-24.3), respectively.
3170 16331510 Class I HLA-A (*0101 and *3101) and HLA-Cw (*0303 and *0501) alleles were significantly associated with measles-virus-induced IFN-gamma secretion.
3171 16331510 HLA-A*3101 and Cw*0303 were associated with a higher median IFN-gamma response, while A*0101 and Cw*0501 were associated with lower measles-specific IFN-gamma response.
3172 16331510 We found limited associations between HLA class I gene polymorphisms and Th2-like (IL-4) immune responses after measles vaccination, indicating that HLA class I molecules may have a limited effect on measles-vaccine-induced IL-4 secretion.
3173 16331510 Immunologic significance of HLA class I genes in measles virus-specific IFN-gamma and IL-4 cytokine immune responses.
3174 16331510 Median values for measles-specific interferon gamma (IFN-gamma) and interleukin-4 (IL-4) cytokines were 40.7 pg/ml [interquartile range (IQR) 8.1-176.7] and 9.7 pg/ml (IQR 2.8-24.3), respectively.
3175 16331510 Class I HLA-A (*0101 and *3101) and HLA-Cw (*0303 and *0501) alleles were significantly associated with measles-virus-induced IFN-gamma secretion.
3176 16331510 HLA-A*3101 and Cw*0303 were associated with a higher median IFN-gamma response, while A*0101 and Cw*0501 were associated with lower measles-specific IFN-gamma response.
3177 16331510 We found limited associations between HLA class I gene polymorphisms and Th2-like (IL-4) immune responses after measles vaccination, indicating that HLA class I molecules may have a limited effect on measles-vaccine-induced IL-4 secretion.
3178 16331510 Immunologic significance of HLA class I genes in measles virus-specific IFN-gamma and IL-4 cytokine immune responses.
3179 16331510 Median values for measles-specific interferon gamma (IFN-gamma) and interleukin-4 (IL-4) cytokines were 40.7 pg/ml [interquartile range (IQR) 8.1-176.7] and 9.7 pg/ml (IQR 2.8-24.3), respectively.
3180 16331510 Class I HLA-A (*0101 and *3101) and HLA-Cw (*0303 and *0501) alleles were significantly associated with measles-virus-induced IFN-gamma secretion.
3181 16331510 HLA-A*3101 and Cw*0303 were associated with a higher median IFN-gamma response, while A*0101 and Cw*0501 were associated with lower measles-specific IFN-gamma response.
3182 16331510 We found limited associations between HLA class I gene polymorphisms and Th2-like (IL-4) immune responses after measles vaccination, indicating that HLA class I molecules may have a limited effect on measles-vaccine-induced IL-4 secretion.
3183 16331519 Between March 1999 and May 2000, 18 HLA-A*0201(+) patients with metastatic melanoma were enrolled in a phase I trial using a dendritic cell (DC) vaccine generated by culturing CD34(+) hematopoietic progenitors.
3184 16331519 The DC vaccine was loaded with four melanoma peptides (MART-1/MelanA, tyrosinase, MAGE-3, and gp100), Influenza matrix peptide (Flu-MP), and keyhole limpet hemocyanin (KLH).
3185 16369867 Target HCV NS3 CD4+ Th1 epitope to major histocompatibility complex class II pathway.
3186 16369867 A hepatitis C virus (HCV) plasmid vaccine was constructed, based on class II-associated invariant chain peptide (CLIP) substitution which endogenously targets HCV non-structure protein 3 (NS3) CD4+ T helper 1(Th1) epitope (1248AA-1261AA) to major histocompatibility complex (MHC) class II antigen.
3187 16375690 Cancer specific immunity elicited with vaccines has traditionally focused on the activation of the CD8 cytolytic T lymphocyte (CTL) often involving direct stimulation of immunity using HLA-class I binding peptide epitopes.
3188 16375690 A major problem is that CD8 T cells alone can not be sustained without the concomitant activation of CD4 T helper (Th) cells.
3189 16385626 Although our results indicate that DC-SIGN is not the major receptor for VLP in DC, this interaction contributes to the activation of DC surface antigens (HLA class I) and of various cytokines/chemokines, particularly TNF-alpha, IL-6, and RANTES.
3190 16389301 We hypothesize that over-expression of transporters associated with antigen processing (TAP1 and TAP2), components of the major histocompatibility complex (MHC) class I antigen-processing pathway, enhances antigen-specific cytotoxic activity in response to viral infection.
3191 16389301 An expression system using recombinant vaccinia virus (VV) was used to over-express human TAP1 and TAP2 (VV-hTAP1,2) in normal mice.
3192 16389301 Mechanistically, the total MHC class I antigen surface expression and the cross-presentation mechanism in spleen-derived dendritic cells was augmented by over-expression of TAP.
3193 16389301 We hypothesize that over-expression of transporters associated with antigen processing (TAP1 and TAP2), components of the major histocompatibility complex (MHC) class I antigen-processing pathway, enhances antigen-specific cytotoxic activity in response to viral infection.
3194 16389301 An expression system using recombinant vaccinia virus (VV) was used to over-express human TAP1 and TAP2 (VV-hTAP1,2) in normal mice.
3195 16389301 Mechanistically, the total MHC class I antigen surface expression and the cross-presentation mechanism in spleen-derived dendritic cells was augmented by over-expression of TAP.
3196 16391848 Their cytotoxicity against HLA-A24+ PSA-expressing colon cancer cells was dependent on HLA class I-restricted and CD8+ T cells.
3197 16407287 We show here a striking example of a nested set of at least three highly antigenic and similarly abundant natural MHC class I ligands, 15, 10, and 9 amino acids in length, derived from a single human immunodeficiency virus gp160 epitope.
3198 16408213 Using computer aided motif predictions for possible HLA class I epitopes, we have identified peptides from Tie-2 that should bind with a range of affinities to HLA-A*0201.
3199 16408213 Moreover, the efficiency of immunisation was increased when we linked CD4 epitopes to CD8 epitopes.
3200 16423040 The effector CD8(+) T cells recognize major histocompatibility complex (MHC) class I binding altered self-peptides expressed in tumour cells.
3201 16423040 Although the requirement for CD4(+) T helper type 1 (Th1) cells in regulating CD8(+) T cells has been documented, their target epitopes and functional impact in antitumour responses remain unclear.
3202 16423040 Coimmunization of mice with Peptide-25 and ovalbumin (OVA) or Peptide-25 and B16 melanoma peptide [tyrosinase-related protein-2 (TRP-2)] for MHC class I led to a profound increase in CD8(+) T cells specific for OVA and TRP-2 peptides, respectively.
3203 16423040 This heightened response depended on Peptide-25-specific CD4(+) T cells and interferon-gamma-producing T cells.
3204 16423040 In tumour protection assays, immunization with Peptide-25 and OVA resulted in the enhancement of CD8(+) cytotoxic cell generation specific for OVA and the growth inhibition of EL-4 thymoma expressing OVA peptide leading to the tumour rejection.
3205 16423040 The effector CD8(+) T cells recognize major histocompatibility complex (MHC) class I binding altered self-peptides expressed in tumour cells.
3206 16423040 Although the requirement for CD4(+) T helper type 1 (Th1) cells in regulating CD8(+) T cells has been documented, their target epitopes and functional impact in antitumour responses remain unclear.
3207 16423040 Coimmunization of mice with Peptide-25 and ovalbumin (OVA) or Peptide-25 and B16 melanoma peptide [tyrosinase-related protein-2 (TRP-2)] for MHC class I led to a profound increase in CD8(+) T cells specific for OVA and TRP-2 peptides, respectively.
3208 16423040 This heightened response depended on Peptide-25-specific CD4(+) T cells and interferon-gamma-producing T cells.
3209 16423040 In tumour protection assays, immunization with Peptide-25 and OVA resulted in the enhancement of CD8(+) cytotoxic cell generation specific for OVA and the growth inhibition of EL-4 thymoma expressing OVA peptide leading to the tumour rejection.
3210 16424052 Tumor cells transduced with the MHC class II Transactivator and CD80 activate tumor-specific CD4+ T cells whether or not they are silenced for invariant chain.
3211 16424052 Because expression of multiple MHC II alleles would facilitate presentation of a broader repertoire of tumor antigens, we have now transduced tumor cells with the MHC class II transactivator (CIITA), a regulatory gene that coordinately increases expression of all MHC II alleles.
3212 16424052 To determine if Ii expression affects presentation of MHC class II-restricted endogenously synthesized tumor antigens in human tumor cells, HLA-DR-MCF10 breast cancer cells were transduced with the CIITA, CD80 costimulatory molecule gene, and with or without small interfering RNAs (siRNA) specific for Ii.
3213 16424052 Ii expression is silenced >95% in CIITA/CD80/siRNA transductants; down-regulation of Ii does not affect HLA-DR expression or stability; and Ii(+) and Ii(-) transductants activate human CD4+ T cells to DRB1*0701-restricted HER-2/neu epitopes.
3214 16424052 Therefore, tumor cells transduced with the CIITA, CD80, and with or without Ii siRNA present endogenously synthesized tumor antigens and are potential vaccines for activating tumor-specific CD4+ T cells.
3215 16424052 Tumor cells transduced with the MHC class II Transactivator and CD80 activate tumor-specific CD4+ T cells whether or not they are silenced for invariant chain.
3216 16424052 Because expression of multiple MHC II alleles would facilitate presentation of a broader repertoire of tumor antigens, we have now transduced tumor cells with the MHC class II transactivator (CIITA), a regulatory gene that coordinately increases expression of all MHC II alleles.
3217 16424052 To determine if Ii expression affects presentation of MHC class II-restricted endogenously synthesized tumor antigens in human tumor cells, HLA-DR-MCF10 breast cancer cells were transduced with the CIITA, CD80 costimulatory molecule gene, and with or without small interfering RNAs (siRNA) specific for Ii.
3218 16424052 Ii expression is silenced >95% in CIITA/CD80/siRNA transductants; down-regulation of Ii does not affect HLA-DR expression or stability; and Ii(+) and Ii(-) transductants activate human CD4+ T cells to DRB1*0701-restricted HER-2/neu epitopes.
3219 16424052 Therefore, tumor cells transduced with the CIITA, CD80, and with or without Ii siRNA present endogenously synthesized tumor antigens and are potential vaccines for activating tumor-specific CD4+ T cells.
3220 16424052 Tumor cells transduced with the MHC class II Transactivator and CD80 activate tumor-specific CD4+ T cells whether or not they are silenced for invariant chain.
3221 16424052 Because expression of multiple MHC II alleles would facilitate presentation of a broader repertoire of tumor antigens, we have now transduced tumor cells with the MHC class II transactivator (CIITA), a regulatory gene that coordinately increases expression of all MHC II alleles.
3222 16424052 To determine if Ii expression affects presentation of MHC class II-restricted endogenously synthesized tumor antigens in human tumor cells, HLA-DR-MCF10 breast cancer cells were transduced with the CIITA, CD80 costimulatory molecule gene, and with or without small interfering RNAs (siRNA) specific for Ii.
3223 16424052 Ii expression is silenced >95% in CIITA/CD80/siRNA transductants; down-regulation of Ii does not affect HLA-DR expression or stability; and Ii(+) and Ii(-) transductants activate human CD4+ T cells to DRB1*0701-restricted HER-2/neu epitopes.
3224 16424052 Therefore, tumor cells transduced with the CIITA, CD80, and with or without Ii siRNA present endogenously synthesized tumor antigens and are potential vaccines for activating tumor-specific CD4+ T cells.
3225 16424181 Therapeutic vaccination of active arthritis with a glycosylated collagen type II peptide in complex with MHC class II molecules.
3226 16424181 In both collagen-induced arthritis (CIA) and rheumatoid arthritis, T cells recognize a galactosylated peptide from type II collagen (CII).
3227 16432254 This is accomplished by culturing virus-infected cells with stable isotope-labeled amino acids that are expected to be anchor residues (i.e. residues of the peptide that have amino acid side chains that bind into pockets lining the peptide-binding groove of the MHC class I molecule) for the human leukocyte antigen allele of interest.
3228 16446175 Culturing in the presence of granulocyte monocyte colony stimulating factor (GM-CSF) increased the in vitro differentiation and maturation of these cells into BM-derived DCs (CD11c+ and MHC class II+).
3229 16446175 Maturation of DCs was determined by increased CD80 and CD86 expression, IL-4 and IL-12 production, reduction in phagocytic capacity and increase in the antigen presenting ability to primed or naïve T lymphocytes.
3230 16450380 Major histocompatibility complex (MHC) peptide binding algorithms were used to predict potential epitopes in PAX3 capable of stimulating in vitro naïve HLA-A0201 restricted cytotoxic T-lymphocytes (CTLs).
3231 16451198 We investigated the genetic diversity of HLA-A, HLA-B and HLA-C alleles in remote populations of Cameroon.
3232 16451198 Subjects from seven small, isolated, indigenous populations (N = 274) in the rainforest of southern Cameroon were typed for HLA-A, HLA-B and HLA-C alleles using a polymerase chain reaction/sequence-specific oligonucleotide probe assay and sequence analysis.
3233 16451198 Multiple alleles of the HLA-A (N = 28), HLA-B (N = 41) and HLA-C (N = 21) loci were identified, of which A*2301[allele frequency (AF) = 12.8%], B*5802 (AF = 10.9%) and Cw*0401 (AF = 16.6%) were the most frequent individual alleles and A*02 (AF = 19.0%), B*58 (AF = 15.9%) and Cw*07 (AF = 22.4%) the most common serologically defined groups of alleles.
3234 16451198 Heterozygosity values of 0.89, 0.92 and 0.89 were determined for HLA-A, HLA-B and HLA-C, respectively.
3235 16451198 We investigated the genetic diversity of HLA-A, HLA-B and HLA-C alleles in remote populations of Cameroon.
3236 16451198 Subjects from seven small, isolated, indigenous populations (N = 274) in the rainforest of southern Cameroon were typed for HLA-A, HLA-B and HLA-C alleles using a polymerase chain reaction/sequence-specific oligonucleotide probe assay and sequence analysis.
3237 16451198 Multiple alleles of the HLA-A (N = 28), HLA-B (N = 41) and HLA-C (N = 21) loci were identified, of which A*2301[allele frequency (AF) = 12.8%], B*5802 (AF = 10.9%) and Cw*0401 (AF = 16.6%) were the most frequent individual alleles and A*02 (AF = 19.0%), B*58 (AF = 15.9%) and Cw*07 (AF = 22.4%) the most common serologically defined groups of alleles.
3238 16451198 Heterozygosity values of 0.89, 0.92 and 0.89 were determined for HLA-A, HLA-B and HLA-C, respectively.
3239 16451198 We investigated the genetic diversity of HLA-A, HLA-B and HLA-C alleles in remote populations of Cameroon.
3240 16451198 Subjects from seven small, isolated, indigenous populations (N = 274) in the rainforest of southern Cameroon were typed for HLA-A, HLA-B and HLA-C alleles using a polymerase chain reaction/sequence-specific oligonucleotide probe assay and sequence analysis.
3241 16451198 Multiple alleles of the HLA-A (N = 28), HLA-B (N = 41) and HLA-C (N = 21) loci were identified, of which A*2301[allele frequency (AF) = 12.8%], B*5802 (AF = 10.9%) and Cw*0401 (AF = 16.6%) were the most frequent individual alleles and A*02 (AF = 19.0%), B*58 (AF = 15.9%) and Cw*07 (AF = 22.4%) the most common serologically defined groups of alleles.
3242 16451198 Heterozygosity values of 0.89, 0.92 and 0.89 were determined for HLA-A, HLA-B and HLA-C, respectively.
3243 16451198 We investigated the genetic diversity of HLA-A, HLA-B and HLA-C alleles in remote populations of Cameroon.
3244 16451198 Subjects from seven small, isolated, indigenous populations (N = 274) in the rainforest of southern Cameroon were typed for HLA-A, HLA-B and HLA-C alleles using a polymerase chain reaction/sequence-specific oligonucleotide probe assay and sequence analysis.
3245 16451198 Multiple alleles of the HLA-A (N = 28), HLA-B (N = 41) and HLA-C (N = 21) loci were identified, of which A*2301[allele frequency (AF) = 12.8%], B*5802 (AF = 10.9%) and Cw*0401 (AF = 16.6%) were the most frequent individual alleles and A*02 (AF = 19.0%), B*58 (AF = 15.9%) and Cw*07 (AF = 22.4%) the most common serologically defined groups of alleles.
3246 16451198 Heterozygosity values of 0.89, 0.92 and 0.89 were determined for HLA-A, HLA-B and HLA-C, respectively.
3247 16455170 KM+ induced a smaller inflammatory reaction in the air pouch model and was able to inhibit differentiation of dendritic cells (BMDC), but to induce maturation by enhancing the expression of MHC II, CD80 and CD86.
3248 16476052 Herein, we demonstrate a comprehensive study utilizing a full spectrum of inhibitors to various pathways of MHC class I to elucidate the mechanism of the membrane translocating peptide, penetratin from Antennapedia (Int).
3249 16476052 It is clear that Int, RQIKIWFQNRRMKWKK when tandemly linked to a cytotoxic T lymphocyte peptide of ovalbumin, SIINFEKL (IntSIIN) is endocytosed via phagocytosis or macropinocytosis by dendritic cells in an ATP-dependent manner and is processed by a proteasome- and tapasin-independent pathway for presentation and loading to MHC class I molecules.
3250 16476052 Herein, we demonstrate a comprehensive study utilizing a full spectrum of inhibitors to various pathways of MHC class I to elucidate the mechanism of the membrane translocating peptide, penetratin from Antennapedia (Int).
3251 16476052 It is clear that Int, RQIKIWFQNRRMKWKK when tandemly linked to a cytotoxic T lymphocyte peptide of ovalbumin, SIINFEKL (IntSIIN) is endocytosed via phagocytosis or macropinocytosis by dendritic cells in an ATP-dependent manner and is processed by a proteasome- and tapasin-independent pathway for presentation and loading to MHC class I molecules.
3252 16481078 To develop a vaccine against hepatitis C virus, we synthesized four long peptides from nonstructural proteins NS3, NS4 and NS5B containing HLA-class I and class II epitopes mainly inducing responses in natural infection.
3253 16481078 HLA-A2.1/HLA-DR1 transgenic mice immunized with one peptide, containing a class II epitope implicated in viral resolution, developed IFNgamma-producing CD4+-T and CD8+-T cells.
3254 16493038 Using cytokine flow cytometry, we have defined four novel HLA-A*02-restricted dengue viral epitopes recognized by up to 1.5% of circulating CD8+ T cells in four donors after primary vaccination.
3255 16493038 Stimulation with variant peptides also altered the relative frequencies of the various subsets of cells that expressed IFN-gamma, TNF-alpha, MIP-1beta, and combinations of these cytokines.
3256 16493065 Apparent loss of memory CD8+ effector function in vivo was supported by a prominent decline in MHC expression on CNS resident target cells, presumably reflecting diminished IFN-gamma.
3257 16493065 These studies demonstrate that vaccine-induced T cell memory alone is unable to control persisting virus in a tissue with strict IFN-dependent MHC regulation, as evident in immune privileged sites.
3258 16513289 Presentation of allergen derived peptides via MHC I and MHC II stimulates specific Th1 responses resulting in high levels of IFN-gamma and IgG.
3259 16515877 The ubiquitin-proteasome system (UPS) plays an indispensable role in inducing MHC class I-restricted CD8+ T cells and was exploited in the development of a DNA vaccine against the intracellular protozoan Toxoplasma gondii by constructing a chimeric DNA encoding a fusion protein between murine ubiquitin and the toxoplasma antigen SAG1.
3260 16515877 Mice vaccinated with the DNA acquired potent protective immunity mediated by MHC class I-restricted CD8+ T cells against infection by the highly virulent Toxoplasma.
3261 16515877 The accelerated degradation and induction of immunity were dependent on the UPS since mice lacking an immuno-subunit of 20S proteasome, LMP7, lost these functions, although they were independent of the proteasome regulator PA28alpha/beta complex.
3262 16515877 The ubiquitin-proteasome system (UPS) plays an indispensable role in inducing MHC class I-restricted CD8+ T cells and was exploited in the development of a DNA vaccine against the intracellular protozoan Toxoplasma gondii by constructing a chimeric DNA encoding a fusion protein between murine ubiquitin and the toxoplasma antigen SAG1.
3263 16515877 Mice vaccinated with the DNA acquired potent protective immunity mediated by MHC class I-restricted CD8+ T cells against infection by the highly virulent Toxoplasma.
3264 16515877 The accelerated degradation and induction of immunity were dependent on the UPS since mice lacking an immuno-subunit of 20S proteasome, LMP7, lost these functions, although they were independent of the proteasome regulator PA28alpha/beta complex.
3265 16524630 Quantitative matrix-based models for prediction of the proteasome cleavage sites in a protein were developed using a training set of 489 naturally processed T-cell epitopes (nonamer peptides) associated with HLA-A and HLA-B molecules.
3266 16531820 This study examined the subset composition and function of specific T cells generated by immunization with MHC class I binding tyrosinase peptides in combination with the adjuvants granulocyte-macrophage colony-stimulating factor and keyhole limpet hemocyanin in peripheral blood (PB) and bone marrow (BM) of melanoma patients.
3267 16531820 BM tyrosinase-specific T cells were functional, because they produced interferon-gamma and had a high proliferative potential.
3268 16533527 Fifty HLA-A*0201 peptides were selected from several target oncoproteins: Wilms' tumor protein (WT1), native and imatinib-mutated bcr-abl p210, JAK2 protein and Ewing's sarcoma fusion protein type 1.
3269 16533753 WT1(235), a ninemer peptide derived from Wilms' tumor gene product, is a candidate peptide for the vaccination of HLA-A*0201-positive patients with hematopoietic malignancies.
3270 16550190 The CTLs target an alternative repertoire of peptide epitopes that emerge in MHC class I at the surface of cells with impaired function of transporter associated with antigen processing (TAP), tapasin or the proteasome.
3271 16552058 Immunization with a circumsporozoite epitope fused to Bordetella pertussis adenylate cyclase in conjunction with cytotoxic T-lymphocyte-associated antigen 4 blockade confers protection against Plasmodium berghei liver-stage malaria.
3272 16552058 The adenylate cyclase toxoid (ACT) of Bordetella pertussis is capable of delivering its N-terminal catalytic domain into the cytosol of CD11b-expressing professional antigen-presenting cells such as myeloid dendritic cells.
3273 16552058 This allows delivery of CD8+ T-cell epitopes to the major histocompatibility complex (MHC) class I presentation pathway.
3274 16552058 Recombinant detoxified ACT containing an epitope of the Plasmodium berghei circumsporozoite protein (CSP), indeed, induced a specific CD8+ T-cell response in immunized mice after a single application, as detected by MHC multimer staining and gamma interferon (IFN-gamma) ELISPOT assay.
3275 16552058 This CSP-specific response could be significantly enhanced by prime-boost immunization with recombinant ACT in combination with anti-CTLA-4 during the boost immunization.
3276 16552058 Immunization with a circumsporozoite epitope fused to Bordetella pertussis adenylate cyclase in conjunction with cytotoxic T-lymphocyte-associated antigen 4 blockade confers protection against Plasmodium berghei liver-stage malaria.
3277 16552058 The adenylate cyclase toxoid (ACT) of Bordetella pertussis is capable of delivering its N-terminal catalytic domain into the cytosol of CD11b-expressing professional antigen-presenting cells such as myeloid dendritic cells.
3278 16552058 This allows delivery of CD8+ T-cell epitopes to the major histocompatibility complex (MHC) class I presentation pathway.
3279 16552058 Recombinant detoxified ACT containing an epitope of the Plasmodium berghei circumsporozoite protein (CSP), indeed, induced a specific CD8+ T-cell response in immunized mice after a single application, as detected by MHC multimer staining and gamma interferon (IFN-gamma) ELISPOT assay.
3280 16552058 This CSP-specific response could be significantly enhanced by prime-boost immunization with recombinant ACT in combination with anti-CTLA-4 during the boost immunization.
3281 16565072 In this study we have evaluated the specificity of the T* sequence with regard to its binding to the human class II MHC protein DR4 (HLA-DRB1*0401), its interactions with antigen receptors on T cells, and the effect of natural variants of this sequence on its immunogenicity.
3282 16565072 Immunization of a human DR4 volunteer with a peptide-based vaccine containing the T* sequence elicited CD4+ T cells that recognize each of these epitopes.
3283 16565072 MHC tetramers carrying DR4/T*-1 MHC-peptide complexes stained and efficiently stimulated these cells in vitro.
3284 16565072 In this study we have evaluated the specificity of the T* sequence with regard to its binding to the human class II MHC protein DR4 (HLA-DRB1*0401), its interactions with antigen receptors on T cells, and the effect of natural variants of this sequence on its immunogenicity.
3285 16565072 Immunization of a human DR4 volunteer with a peptide-based vaccine containing the T* sequence elicited CD4+ T cells that recognize each of these epitopes.
3286 16565072 MHC tetramers carrying DR4/T*-1 MHC-peptide complexes stained and efficiently stimulated these cells in vitro.
3287 16571416 We found that 31 of 110 HIV-1 peptides bound to HLA-A*2603 and that only two peptides (Gag169-177 and Env63-72) induced specific CD8+T cells by stimulating peripheral blood mononuclear leukocytes from HIV-1-infected individuals carrying HLA-A*2603.
3288 16571416 Gag169-177-specific CD8+T cells were frequently detected in both HLA-A*2601+ and -A*2603+ individuals with chronic HIV-1 infection, whereas Env63-72-specific ones were frequently detected only in the HLA-A*2603+ individuals.
3289 16571416 We found that 31 of 110 HIV-1 peptides bound to HLA-A*2603 and that only two peptides (Gag169-177 and Env63-72) induced specific CD8+T cells by stimulating peripheral blood mononuclear leukocytes from HIV-1-infected individuals carrying HLA-A*2603.
3290 16571416 Gag169-177-specific CD8+T cells were frequently detected in both HLA-A*2601+ and -A*2603+ individuals with chronic HIV-1 infection, whereas Env63-72-specific ones were frequently detected only in the HLA-A*2603+ individuals.
3291 16583211 To test whether HLA-A*0279 has the ability to cross-present A*0201 - restricted peptides to T cells, the full lenght cDNA of HLA-A*0201, -A* 020601 and -A*0279 were respectively transfected into COS-7 cells, which were then used as targets in IFN-gamma release Elispot assay.
3292 16583780 Current quantitative trait loci for nematode resistance include the MHC genes, interferon gamma gene, IgE gene and microsatellites on chromosome 1, 5 and 6.
3293 16585547 By depleting CD4+ and CD8+ cell populations before tumor challenge, we identify CD8+ cells as the main effector cells involved in tumor eradication.
3294 16585547 We show that Fc gammaRI and Fc gammaRIII are capable of enhancing MHC class I-restricted Ag presentation to CD8+ T cells in vitro and that these activating Fc gammaRs on DCs are required for efficient priming of Ag-specific CD8+ cells in vivo and induction of tumor protection.
3295 16585577 The importance of the site of Ag localization within microbial pathogens for the effective generation of CD8+ T cells has been studied extensively, generally supporting the view that Ag secretion within infected target cells is required for optimal MHC class I-restricted Ag presentation.
3296 16585577 In contrast, relatively little is known about the importance of pathogen Ag localization for the activation of MHC class II-restricted CD4+ T cells, despite their clear importance for host protection.
3297 16585577 The importance of the site of Ag localization within microbial pathogens for the effective generation of CD8+ T cells has been studied extensively, generally supporting the view that Ag secretion within infected target cells is required for optimal MHC class I-restricted Ag presentation.
3298 16585577 In contrast, relatively little is known about the importance of pathogen Ag localization for the activation of MHC class II-restricted CD4+ T cells, despite their clear importance for host protection.
3299 16597462 Secondary anchor substitutions in an HLA-A*0201-restricted T-cell epitope derived from Her-2/neu.
3300 16597462 We investigated analogues of GP2 (IISAVVGIL), an HLA-A*0201-restricted T-cell epitope derived from residues 654-662 in the tumor-associated antigen (TAA) Her-2/neu.
3301 16597462 Secondary anchor substitutions in an HLA-A*0201-restricted T-cell epitope derived from Her-2/neu.
3302 16597462 We investigated analogues of GP2 (IISAVVGIL), an HLA-A*0201-restricted T-cell epitope derived from residues 654-662 in the tumor-associated antigen (TAA) Her-2/neu.
3303 16622680 We analysed six cell lines established from different metastases of melanoma patient UKRV-Mel-20 for specific characteristics known to have an impact on the tumor-T cell interaction: (1) alterations in the HLA class I phenotype, (2) expression of Fas/CD95, and (3) expression of specific cytokines and chemokines.
3304 16622680 One of the cell lines, UKRV-Mel-20f, exhibited an HLA class I haplotype loss and just this cell line was also characterised by the expression of Fas/CD95 and of relatively high levels of proinflammatory chemokines suggesting that the cytotoxic activity of tumor-infiltrating T cells might have selected the outgrowth of this tumor cell variant.
3305 16622680 All other cell lines analysed showed no alterations in HLA class I expression, but, in contrast to UKRV-Mel-20f, expressed much lower levels of Fas/CD95 and of proinflammatory chemokines and some of them produced high levels of immunosuppressive TGF-beta1.
3306 16622680 We analysed six cell lines established from different metastases of melanoma patient UKRV-Mel-20 for specific characteristics known to have an impact on the tumor-T cell interaction: (1) alterations in the HLA class I phenotype, (2) expression of Fas/CD95, and (3) expression of specific cytokines and chemokines.
3307 16622680 One of the cell lines, UKRV-Mel-20f, exhibited an HLA class I haplotype loss and just this cell line was also characterised by the expression of Fas/CD95 and of relatively high levels of proinflammatory chemokines suggesting that the cytotoxic activity of tumor-infiltrating T cells might have selected the outgrowth of this tumor cell variant.
3308 16622680 All other cell lines analysed showed no alterations in HLA class I expression, but, in contrast to UKRV-Mel-20f, expressed much lower levels of Fas/CD95 and of proinflammatory chemokines and some of them produced high levels of immunosuppressive TGF-beta1.
3309 16622680 We analysed six cell lines established from different metastases of melanoma patient UKRV-Mel-20 for specific characteristics known to have an impact on the tumor-T cell interaction: (1) alterations in the HLA class I phenotype, (2) expression of Fas/CD95, and (3) expression of specific cytokines and chemokines.
3310 16622680 One of the cell lines, UKRV-Mel-20f, exhibited an HLA class I haplotype loss and just this cell line was also characterised by the expression of Fas/CD95 and of relatively high levels of proinflammatory chemokines suggesting that the cytotoxic activity of tumor-infiltrating T cells might have selected the outgrowth of this tumor cell variant.
3311 16622680 All other cell lines analysed showed no alterations in HLA class I expression, but, in contrast to UKRV-Mel-20f, expressed much lower levels of Fas/CD95 and of proinflammatory chemokines and some of them produced high levels of immunosuppressive TGF-beta1.
3312 16630140 As these expression profiles and functional features of SCRN1 appeared to be compatible with the characteristics of the hypothesized ideal TAAs, we examined whether SCRN1 protein contains antigenic epitope peptides restricted to HLA-A*0201.
3313 16630140 The CTL clones were successfully induced with a peptide SCRN1-196 (KMDAEHPEL), and they lyzed not only the peptide-pulsed targets but also the tumor cells expressing both SCRN1 and HLA-A*0201 endogenously.
3314 16630140 As these expression profiles and functional features of SCRN1 appeared to be compatible with the characteristics of the hypothesized ideal TAAs, we examined whether SCRN1 protein contains antigenic epitope peptides restricted to HLA-A*0201.
3315 16630140 The CTL clones were successfully induced with a peptide SCRN1-196 (KMDAEHPEL), and they lyzed not only the peptide-pulsed targets but also the tumor cells expressing both SCRN1 and HLA-A*0201 endogenously.
3316 16646078 CD8 T-cell recognition of human 5T4 oncofetal antigen.
3317 16646078 Here, we report the generation of human CD8 T cells specific for the 5T4 antigen by stimulation with autologous monocyte derived DC infected with a replication defective adenovirus encoding the 5T4 cDNA (Ad5T4).
3318 16646078 In a parallel approach, incorporating the results of proteasome-mediated digestion of 5T4 derived 35-mer peptides and the potential high affinity epitopes predicted by a computer-based algorithm, we identified 8 putative HLA-A*0201-presented CD8 MHC class I epitopes of 5T4 antigen.
3319 16646078 Two of these generated specific CD8 T cells after restimulation with peptide loaded autologous DC and assay by cytotoxicity and IFN gamma ELISPOT.
3320 16646078 Moreover these particular peptide generated T cells recognized naturally 5T4 positive tumor cells only if they expressed HLA-A*0201 as judged by IFN gamma ELISPOT or ELISA.
3321 16646078 Also, HLA-A*0201 CD8 T cells recognized these peptides in a DC-Ad5T4 polyclonal response.
3322 16646078 In conclusion, there is a repertoire of CD8 T cell recognition of 5T4 in normal human donors and some candidate HLA-A*0201 epitopes have been identified.
3323 16646078 CD8 T-cell recognition of human 5T4 oncofetal antigen.
3324 16646078 Here, we report the generation of human CD8 T cells specific for the 5T4 antigen by stimulation with autologous monocyte derived DC infected with a replication defective adenovirus encoding the 5T4 cDNA (Ad5T4).
3325 16646078 In a parallel approach, incorporating the results of proteasome-mediated digestion of 5T4 derived 35-mer peptides and the potential high affinity epitopes predicted by a computer-based algorithm, we identified 8 putative HLA-A*0201-presented CD8 MHC class I epitopes of 5T4 antigen.
3326 16646078 Two of these generated specific CD8 T cells after restimulation with peptide loaded autologous DC and assay by cytotoxicity and IFN gamma ELISPOT.
3327 16646078 Moreover these particular peptide generated T cells recognized naturally 5T4 positive tumor cells only if they expressed HLA-A*0201 as judged by IFN gamma ELISPOT or ELISA.
3328 16646078 Also, HLA-A*0201 CD8 T cells recognized these peptides in a DC-Ad5T4 polyclonal response.
3329 16646078 In conclusion, there is a repertoire of CD8 T cell recognition of 5T4 in normal human donors and some candidate HLA-A*0201 epitopes have been identified.
3330 16646078 CD8 T-cell recognition of human 5T4 oncofetal antigen.
3331 16646078 Here, we report the generation of human CD8 T cells specific for the 5T4 antigen by stimulation with autologous monocyte derived DC infected with a replication defective adenovirus encoding the 5T4 cDNA (Ad5T4).
3332 16646078 In a parallel approach, incorporating the results of proteasome-mediated digestion of 5T4 derived 35-mer peptides and the potential high affinity epitopes predicted by a computer-based algorithm, we identified 8 putative HLA-A*0201-presented CD8 MHC class I epitopes of 5T4 antigen.
3333 16646078 Two of these generated specific CD8 T cells after restimulation with peptide loaded autologous DC and assay by cytotoxicity and IFN gamma ELISPOT.
3334 16646078 Moreover these particular peptide generated T cells recognized naturally 5T4 positive tumor cells only if they expressed HLA-A*0201 as judged by IFN gamma ELISPOT or ELISA.
3335 16646078 Also, HLA-A*0201 CD8 T cells recognized these peptides in a DC-Ad5T4 polyclonal response.
3336 16646078 In conclusion, there is a repertoire of CD8 T cell recognition of 5T4 in normal human donors and some candidate HLA-A*0201 epitopes have been identified.
3337 16646078 CD8 T-cell recognition of human 5T4 oncofetal antigen.
3338 16646078 Here, we report the generation of human CD8 T cells specific for the 5T4 antigen by stimulation with autologous monocyte derived DC infected with a replication defective adenovirus encoding the 5T4 cDNA (Ad5T4).
3339 16646078 In a parallel approach, incorporating the results of proteasome-mediated digestion of 5T4 derived 35-mer peptides and the potential high affinity epitopes predicted by a computer-based algorithm, we identified 8 putative HLA-A*0201-presented CD8 MHC class I epitopes of 5T4 antigen.
3340 16646078 Two of these generated specific CD8 T cells after restimulation with peptide loaded autologous DC and assay by cytotoxicity and IFN gamma ELISPOT.
3341 16646078 Moreover these particular peptide generated T cells recognized naturally 5T4 positive tumor cells only if they expressed HLA-A*0201 as judged by IFN gamma ELISPOT or ELISA.
3342 16646078 Also, HLA-A*0201 CD8 T cells recognized these peptides in a DC-Ad5T4 polyclonal response.
3343 16646078 In conclusion, there is a repertoire of CD8 T cell recognition of 5T4 in normal human donors and some candidate HLA-A*0201 epitopes have been identified.
3344 16646843 We investigated all combinations of six classification methods (classification trees, artificial neural networks, support vector machines, as well as the more recently devised ensemble methods (bagging, random forests, boosting) with four peptide representation schemes (amino acid sequence, select biophysical properties, select quantitative structure-activity relationship (QSAR) descriptors, and the combination of the latter two) in predicting peptide binding to an MHC class I molecule (HLA-A2) and MHC class II molecule (HLA-DR4).
3345 16673447 CD4 T cell help is required for primary CD8 T cell responses to vesicular antigen delivered to dendritic cells in vivo.
3346 16673447 We examined the effectiveness of free antigen as well as antigen with lipopolysaccharide, emulsified in complete Freund's adjuvant, and antigen encapsulated in liposomes in activating adoptively transferred antigen-specific CD4 and CD8 T cells.
3347 16673447 When contained in liposomes, 100- to 1000-fold lower antigen amounts were as efficient in inducing proliferation and effector functions of CD4 and CD8 T cells in draining lymph nodes as other antigen forms.
3348 16673447 CD11c(+)/CD11b(+)/CD205(mod)/CD8alpha(-) DC that captured liposomes were activated and presented this form of antigen in an MHC class I- and class II-restricted manner.
3349 16673447 Primary expansion and cytotoxic activity of CD8 T cells were CD4 T cell-dependent and required the transporter associated with antigen processing (TAP).
3350 16673447 Finally, adoptively transferred CD4 and CD8 T cells were not deleted after primary immunization and rapidly responded to a secondary immunization with antigen-containing liposomes.
3351 16673447 In conclusion, encapsulation of antigen in liposomes is an efficient way of delivering antigen to DC for priming of both CD4 and CD8 T cell responses.
3352 16673447 Importantly, primary CD8 T cell responses were CD4 T cell-dependent.
3353 16678311 OprI activated porcine monocyte-derived dendritic cells (MoDC), upregulating CD80/86 and MHC class II expression, as well as pro-inflammatory cytokines.
3354 16703666 Augmentation of epitope presentation by MHC I is thought to be effected by the immunoproteasome, induced in response to IFN-gamma (interferon-gamma) in some cells, and constitutively expressed in others.
3355 16703666 The authors show that Tat deregulates the balance of the three proteins, LMP2 (low-molecular-mass polypeptide 2), LMP7 and MECL1 (multicatalytic endopeptidase complex-like 1), which distinguish the immunoproteasome from the proteasome, and they provide a molecular explanation.
3356 16703666 Intracellular Tat sequesters IRF-1 (interferon-regulatory factor-1) from its cognate promoter element, where normally it associates with STAT1 (signal transducer and activator of transcription 1) to activate basal transcription of the LMP2 gene.
3357 16707472 For minor histocompatibility antigens HA-1 and HA-2, normal cell expression is restricted to hemopoietic cells, and boosting the immune response to these antigens may potentiate graft-versus-leukemia effect without accompanying graft-versus-host disease.
3358 16707472 To increase efficacy, expansion of HA-1- or HA-2-specific CTL before transplantation is desirable.
3359 16707472 However, primary HA-1- or HA-2-specific CTL expanded in vitro are often of low avidity.
3360 16707472 For clinical application, we constructed vaccines encoding HLA-A*0201-restricted peptides from human HA-1 and HA-2, which were fused to DOM, and tested their performance in HLA-A*0201-transgenic mice.
3361 16707472 Strikingly, these mouse T cells efficiently killed human lymphoblastoid cell lines expressing endogenous HA-1 or HA-2.
3362 16707472 High avidity is indicated by the independence of cytolysis from CD8/MHC class I interaction.
3363 16707472 These safe epitope-specific vaccines offer a potential strategy to prime HA-1- or HA-2-specific CTL in transplant donors before adoptive transfer.
3364 16707472 For minor histocompatibility antigens HA-1 and HA-2, normal cell expression is restricted to hemopoietic cells, and boosting the immune response to these antigens may potentiate graft-versus-leukemia effect without accompanying graft-versus-host disease.
3365 16707472 To increase efficacy, expansion of HA-1- or HA-2-specific CTL before transplantation is desirable.
3366 16707472 However, primary HA-1- or HA-2-specific CTL expanded in vitro are often of low avidity.
3367 16707472 For clinical application, we constructed vaccines encoding HLA-A*0201-restricted peptides from human HA-1 and HA-2, which were fused to DOM, and tested their performance in HLA-A*0201-transgenic mice.
3368 16707472 Strikingly, these mouse T cells efficiently killed human lymphoblastoid cell lines expressing endogenous HA-1 or HA-2.
3369 16707472 High avidity is indicated by the independence of cytolysis from CD8/MHC class I interaction.
3370 16707472 These safe epitope-specific vaccines offer a potential strategy to prime HA-1- or HA-2-specific CTL in transplant donors before adoptive transfer.
3371 16707474 In contrast to mHER-2(9(435)), vaccination of HLA-A*0201 transgenic (HHD) mice with hHER-2(9(435)) significantly increased the frequency of mHER-2(9(435))-specific CTL and also induced strong protective and therapeutic immunity against the transplantable ALC tumor cell line transfected to coexpress HLA-A*0201 and hHER-2/neu or rHER-2/neu.
3372 16707474 Adoptive transfer of CD8(+) CTL from mice immunized with hHER-2(9(435)) efficiently protected naive syngeneic mice inoculated with ALC tumors.
3373 16709828 Here we identified an agonist variant of the SL9 peptide, p41 (SLYNTVAAL), by screening a large synthetic combinatorial nonapeptide library with ex vivo-primed SL9-specific T cells. p41 invariably immunized SL9-cross-reactive CTLs from other donors ex vivo and H-2Db beta2m double knockout mice expressing a chimeric HLA-A*0201/H2-Db MHC class I molecule.
3374 16738849 Previously, we reported the identification of a novel highly immunogenic HLA-A*0201-restricted Prostatic Acid Phosphatase-derived peptide (PAP-3) by a two-step in vivo screening in an HLA-transgenic (HHD) mouse system.
3375 16738849 The 3LL murine Lewis lung carcinoma clone D122 transduced to express HLA-A*0201 and PAP served as a platform for these models.
3376 16738849 The HLA-A*0201-PAP-3 complex specific recombinant single chain scFV-PAP-3 antibodies were generated and used to confirm an endogenous PAP processing resulting in PAP-3 presentation by HLA-A*0201.
3377 16738849 Previously, we reported the identification of a novel highly immunogenic HLA-A*0201-restricted Prostatic Acid Phosphatase-derived peptide (PAP-3) by a two-step in vivo screening in an HLA-transgenic (HHD) mouse system.
3378 16738849 The 3LL murine Lewis lung carcinoma clone D122 transduced to express HLA-A*0201 and PAP served as a platform for these models.
3379 16738849 The HLA-A*0201-PAP-3 complex specific recombinant single chain scFV-PAP-3 antibodies were generated and used to confirm an endogenous PAP processing resulting in PAP-3 presentation by HLA-A*0201.
3380 16738849 Previously, we reported the identification of a novel highly immunogenic HLA-A*0201-restricted Prostatic Acid Phosphatase-derived peptide (PAP-3) by a two-step in vivo screening in an HLA-transgenic (HHD) mouse system.
3381 16738849 The 3LL murine Lewis lung carcinoma clone D122 transduced to express HLA-A*0201 and PAP served as a platform for these models.
3382 16738849 The HLA-A*0201-PAP-3 complex specific recombinant single chain scFV-PAP-3 antibodies were generated and used to confirm an endogenous PAP processing resulting in PAP-3 presentation by HLA-A*0201.
3383 16740768 CIITA-induced MHC class II expression in mammary adenocarcinoma leads to a Th1 polarization of the tumor microenvironment, tumor rejection, and specific antitumor memory.
3384 16775358 A highly restricted T-cell receptor dominates the CD8+ T-cell response to parvovirus B19 infection in HLA-A*2402-positive individuals.
3385 16775358 Six of seven HLA-A*2402-positive individuals with acute parvovirus B19 infections made vigorous CD8-positive cytotoxic T-cell (CTL) responses to the viral epitope FYTPLADQF.
3386 16775358 A highly restricted T-cell receptor dominates the CD8+ T-cell response to parvovirus B19 infection in HLA-A*2402-positive individuals.
3387 16775358 Six of seven HLA-A*2402-positive individuals with acute parvovirus B19 infections made vigorous CD8-positive cytotoxic T-cell (CTL) responses to the viral epitope FYTPLADQF.
3388 16793161 In addition to imparting significant buffering ability to these cationic microparticles, flow cytometry studies indicate that these DNA loaded microparticles significantly up regulate CD80 and MHC class II markers in phagocytic RAW264.7 cells, indicating intrinsic adjuvant effects.
3389 16793181 Thus, broad CMI was induced by OSP in different experimental settings, using different immunogens, without identifying either epitopes or MHC backgrounds of the vaccinees.
3390 16793312 Cells infected with the double sseC sopB, phoP sopB and aroA sopB mutants also exhibited higher expression of MHC, CD80, CD86 and CD54 molecules, and showed a stronger capacity to process and present an I-E(d)-restricted epitope from the influenza hemagglutinin (HA) to CD4+ cells from TCR-HA transgenic mice in vitro.
3391 16818758 High-affinity interactions between peptides and heat shock protein 70 augment CD8+ T lymphocyte immune responses.
3392 16818758 Exogenously delivered antigenic peptides complexed to heat shock proteins (HSPs) are able to enter the endogenous Ag-processing pathway and prime CD8+ CTL.
3393 16818758 It was determined previously that a hybrid peptide containing a MHC class I-binding epitope and HSP70-binding sequence Javelin (J0) in complex with HSP70 could induce cytotoxic T cell responses in vivo that were more robust than those induced by the minimal epitope complexed with HSP70.
3394 16831093 New CD4+ and CD8+ T cell responses induced in chronically HIV type-1-infected patients after immunizations with an HIV type 1 lipopeptide vaccine.
3395 16831093 We showed that an anti-HIV lipopeptide vaccine injected to HIV-uninfected volunteers was well tolerated and able to induce a specific CD4(+) and CD8(+) T cell responses.
3396 16831093 The IFN-gamma secretion by activated CD8(+) T cells was evaluated, using an ex vivo ELISpot assay and 60 CD8(+) T cell epitopes derived from the vaccine.
3397 16831093 These HIV-1 epitopes were detected in patients with various HLA class I molecules (HLA-A2, -A3/A11, -A24, -B7 superfamily, -B8), as found in the majority of the white population.
3398 16831093 The majority of these responders induced specific new CD4(+) and CD8(+) T cell responses.
3399 16840777 Sequential proteolytic processing of the capsular Caf1 antigen of Yersinia pestis for major histocompatibility complex class II-restricted presentation to T lymphocytes.
3400 16840777 We studied the mechanisms of antigen presentation of CD4 T cell epitopes of the capsular Caf1 antigen of Yersinia pestis using murine bone marrow macrophages as antigen presenting cells and T cell hybridomas specific for major histocompatibility complex (MHC) class II-restricted epitopes distributed throughout the Caf1 sequence.
3401 16840777 The data revealed diversity in the pathways used and the degrees of antigen processing required depending on the structural context of epitopes within the Caf1 molecule.
3402 16840777 A fourth epitope located between the two regions of Caf1 showed intermediate behavior.
3403 16840777 The Caf1 capsular protein is a component of second generation plague vaccines and an understanding of the mechanisms and pathways of MHC class II-restricted presentation of multiple epitopes from this candidate vaccine antigen should inform the choice of delivery systems and adjuvants that target vaccines successfully to appropriate intracellular locations to induce protective immune responses against as wide a T cell repertoire as possible.
3404 16840777 Sequential proteolytic processing of the capsular Caf1 antigen of Yersinia pestis for major histocompatibility complex class II-restricted presentation to T lymphocytes.
3405 16840777 We studied the mechanisms of antigen presentation of CD4 T cell epitopes of the capsular Caf1 antigen of Yersinia pestis using murine bone marrow macrophages as antigen presenting cells and T cell hybridomas specific for major histocompatibility complex (MHC) class II-restricted epitopes distributed throughout the Caf1 sequence.
3406 16840777 The data revealed diversity in the pathways used and the degrees of antigen processing required depending on the structural context of epitopes within the Caf1 molecule.
3407 16840777 A fourth epitope located between the two regions of Caf1 showed intermediate behavior.
3408 16840777 The Caf1 capsular protein is a component of second generation plague vaccines and an understanding of the mechanisms and pathways of MHC class II-restricted presentation of multiple epitopes from this candidate vaccine antigen should inform the choice of delivery systems and adjuvants that target vaccines successfully to appropriate intracellular locations to induce protective immune responses against as wide a T cell repertoire as possible.
3409 16849488 Because memory CD8 T cells exhibit a high heterogeneity in terms of phenotype and functional characteristic, we investigated the frequency, phenotype, and functional properties of Ag85A epitope-specific HLA-A*0201 CD8 T cells in children affected by tuberculosis (TB) before and 4 mo after chemotherapy and healthy contact children.
3410 16849488 Using Ag85A peptide/HLA-A*0201 pentamer, we found a low frequency of blood peptide-specific CD8 T cells in tuberculous children before therapy, which consistently increased after therapy to levels detected in healthy contacts.
3411 16849488 Accordingly, pentamer-specific CD8 T cells from tuberculous patients produced low levels of IFN-gamma and had low expression of perforin, which recovered after therapy.
3412 16849488 Because memory CD8 T cells exhibit a high heterogeneity in terms of phenotype and functional characteristic, we investigated the frequency, phenotype, and functional properties of Ag85A epitope-specific HLA-A*0201 CD8 T cells in children affected by tuberculosis (TB) before and 4 mo after chemotherapy and healthy contact children.
3413 16849488 Using Ag85A peptide/HLA-A*0201 pentamer, we found a low frequency of blood peptide-specific CD8 T cells in tuberculous children before therapy, which consistently increased after therapy to levels detected in healthy contacts.
3414 16849488 Accordingly, pentamer-specific CD8 T cells from tuberculous patients produced low levels of IFN-gamma and had low expression of perforin, which recovered after therapy.
3415 16857732 Critical role for serum opsonins and complement receptors CR3 (CD11b/CD18) and CR4 (CD11c/CD18) in phagocytosis of Francisella tularensis by human dendritic cells (DC): uptake of Francisella leads to activation of immature DC and intracellular survival of the bacteria.
3416 16857732 We demonstrate that complement factor C3-derived opsonins and the major complement receptors expressed by DC, the integrins CR3 (CD11b/CD18) and CR4 (CD11c/CD18), play a critical role in this adhesion-mediated phagocytosis.
3417 16857732 LVS induced proinflammatory cytokine production and up-regulation of costimulatory surface proteins (CD40, CD86, and MHC Class II) on DC but resisted killing.
3418 16857732 Serum-treated LVS rapidly induced (within 6 h) a number of cytokines including IL-10, a potent suppressor of macrophage functions and down-regulator of Th1-like responses and the Th1 response inducer IL-12.
3419 16857732 These results suggest that the simultaneous production of an activating (IL-12, IL-1beta, and TNF-alpha) and a suppressing (IL-10) cytokine profile could contribute to the immunopathogenesis of tularemia.
3420 16860448 Moreover, MHC peptide antibodies could block the recognition of peptide-presenting dendritic cells by IMP(58-66)-specific T-cells in a dose dependent manner.
3421 16872625 HLA class I mono-specific APCs and target cells: a method to standardise in vitro CD8+ T cell expansion and functional assays.
3422 16872625 HLA class I mono-specific cells promoted the in vitro expansion of CMV epitope specific CD8+ T cells from 0.03% to 30.6% in 2 weeks, which was comparable to using peptide-loaded dendritic cells.
3423 16872625 HLA class I mono-specific APCs and target cells: a method to standardise in vitro CD8+ T cell expansion and functional assays.
3424 16872625 HLA class I mono-specific cells promoted the in vitro expansion of CMV epitope specific CD8+ T cells from 0.03% to 30.6% in 2 weeks, which was comparable to using peptide-loaded dendritic cells.
3425 16882705 However, HLA-C-restricted CTLs were unaffected by Nef, consistent with down-regulation of cell-surface HLA-A and -B but not HLA-C molecules.
3426 16882705 Thus, CTLs vary dramatically in their susceptibility to Nef interference, suggesting differences in the relative importance of HLA-A- and HLA-B- versus HLA-C-restricted CTLs in vivo.
3427 16882705 However, HLA-C-restricted CTLs were unaffected by Nef, consistent with down-regulation of cell-surface HLA-A and -B but not HLA-C molecules.
3428 16882705 Thus, CTLs vary dramatically in their susceptibility to Nef interference, suggesting differences in the relative importance of HLA-A- and HLA-B- versus HLA-C-restricted CTLs in vivo.
3429 16887973 The antigenicity of nine peptides which could refold with HLA-A*0201 molecules was assessed with an IFN-gamma ELISPOT assay to determine the capacity to stimulate CTLs from PBMCs of HLA-A2(+) SARS-recovered donors.
3430 16887973 A novel HLA-A*0201-restricted decameric epitope P15 (S411-420, KLPDDFMGCV) derived from the S protein was identified and found to localize within the angiotensin-converting enzyme 2 receptor-binding region of the S1 domain.
3431 16887973 P15 could significantly enhance the expression of HLA-A*0201 molecules on the T2 cell surface, stimulate IFN-gamma-producing CTLs from the PBMCs of former SARS patients, and induce specific CTLs from P15-immunized HLA-A2.1 transgenic mice in vivo.
3432 16887973 The antigenicity of nine peptides which could refold with HLA-A*0201 molecules was assessed with an IFN-gamma ELISPOT assay to determine the capacity to stimulate CTLs from PBMCs of HLA-A2(+) SARS-recovered donors.
3433 16887973 A novel HLA-A*0201-restricted decameric epitope P15 (S411-420, KLPDDFMGCV) derived from the S protein was identified and found to localize within the angiotensin-converting enzyme 2 receptor-binding region of the S1 domain.
3434 16887973 P15 could significantly enhance the expression of HLA-A*0201 molecules on the T2 cell surface, stimulate IFN-gamma-producing CTLs from the PBMCs of former SARS patients, and induce specific CTLs from P15-immunized HLA-A2.1 transgenic mice in vivo.
3435 16887973 The antigenicity of nine peptides which could refold with HLA-A*0201 molecules was assessed with an IFN-gamma ELISPOT assay to determine the capacity to stimulate CTLs from PBMCs of HLA-A2(+) SARS-recovered donors.
3436 16887973 A novel HLA-A*0201-restricted decameric epitope P15 (S411-420, KLPDDFMGCV) derived from the S protein was identified and found to localize within the angiotensin-converting enzyme 2 receptor-binding region of the S1 domain.
3437 16887973 P15 could significantly enhance the expression of HLA-A*0201 molecules on the T2 cell surface, stimulate IFN-gamma-producing CTLs from the PBMCs of former SARS patients, and induce specific CTLs from P15-immunized HLA-A2.1 transgenic mice in vivo.
3438 16907911 The methodology [currently presented for cytomegalovirus human leucocyte antigen (HLA)-A2 cognant peptide antigens] allows simultaneous ex vivo quantification of activated (cytokine-producing) and inactive tetramer-positive T cells following HLA class I/peptide/CD28 stimulation independent of endogenous antigen presentation.
3439 16912286 We identified three peptides (GPC(42-50), GLVGLVTFL; GPC(60-68), SLYKGVYEL; and GPC(441-449), YLISIFLHL) that displayed high-affinity binding (< or =98 nM) to HLA-A*0201, induced CD8(+) T-cell responses of high functional avidity in HLA-A*0201 transgenic mice, and were naturally processed from native LASV GPC in human HLA-A*0201-positive target cells.
3440 16917781 BMDCs activated with PLPs up-regulated CD40, CD80, CD86 and major histocompatibility complex (MHC) class II surface markers and produced proinflammatory cytokines.
3441 16917781 Chimeric PLPs [expressing the ovalbumin (OVA)-peptides OVA(257-264) or OVA(323-339)], but not wildtype PLPs, activated OVA-specific CD8 T cells and OVA-specific CD4 T cells, respectively, indicating both MHC class I and II presentation of the peptides by antigen-presenting cells.
3442 16917781 BMDCs activated with PLPs up-regulated CD40, CD80, CD86 and major histocompatibility complex (MHC) class II surface markers and produced proinflammatory cytokines.
3443 16917781 Chimeric PLPs [expressing the ovalbumin (OVA)-peptides OVA(257-264) or OVA(323-339)], but not wildtype PLPs, activated OVA-specific CD8 T cells and OVA-specific CD4 T cells, respectively, indicating both MHC class I and II presentation of the peptides by antigen-presenting cells.
3444 16918359 Human cytotoxic T lymphocytes (CTLs) which could specifically lyse WT1-expressing tumor cells with HLA class I restriction were generated in vitro.
3445 16918359 CD8+ WT1-specific CTLs were also detected in peripheral blood or tumor-draining lymph nodes of cancer patients.
3446 16930710 For a given virus, we use algorithms computing: peptide cleavage probability, transfer through TAP and MHC binding for a large number of HLA alleles.
3447 16932347 Seventeen novel BCR-ABL fusion peptides were identified to bind efficiently to the human lymphocyte antigen (HLA)-A68, HLA-B51, HLA-B61 or HLA-Cw4 HLA class I molecules.
3448 16934904 Investigation of the phenotype of responding lymphocytes showed a response of CD4(+)CD8(+)MHC-class-II(+) cells, identifying them as activated T-helper cells.
3449 16942487 In this study, we developed a novel strategy for the APC to efficiently cross-present a fusion tumour antigen, which contains both MHC class I-restricted and class II-restricted T-cell epitopes from Her-2/neu and p53 in a cognate manner.
3450 16942487 The N-terminus of the fusion Her-2/neu, p53 protein was linked to the sequence encoding for human secondary lymphoid-tissue chemokine for secretion and chemokinesis, and the C-terminus of the fusion protein was linked to a cell-binding domain of IgG (Fc portion, the cell-binding domain of IgG) for receptor-mediated internalization.
3451 16947023 Pancreatic cancer is being pursued as an immunotherapy target using antigen-specific vaccine approaches activating CD8(+) CTL and CD4(+) T-helper cells.
3452 16947023 CD8(+) CTL exert their anti-tumor effects in an HLA-restricted manner and only tumor cells carrying a matched HLA class I sub-type are targets for antigen-specific CTL.
3453 16971487 Here, we describe an approach to enhance immunogenicity that involves the activation of NF-kappaB by the transgenic expression of an intracellular signaling molecule, NF-kappaB-inducing kinase (NIK).
3454 16971487 In vitro, NIK increases dendritic cell antigen presentation in allogeneic and antigen-specific T cell proliferation assays by potently activating NF-kappaB and consequently up-regulating the expression of cytokines (TNF-alpha, IL-6, IL-12, IL-15, and IL-18), chemokines [IL-8, RANTES (regulated on activation, normal T cell expressed and secreted), macrophage inflammatory protein-1alpha, monocyte chemoattractant protein-1, and monocyte chemoattractant protein-3], MHC antigen-presenting molecules (class I and II), and costimulatory molecules (CD80 and CD86).
3455 16971487 In vivo, NIK enhances immune responses against a vector-encoded antigen and shifts them toward a T helper 1 immune response with increased IgG2a levels, T cell proliferation, IFN-gamma production, and cytotoxic T lymphocyte responses more potently than complete Freund's adjuvant, a very efficacious T helper 1-inducing adjuvant.
3456 16971487 These findings define NIK, and possibly other inducers of NF-kappaB activation, as a potent adjuvant strategy that offers great potential for genetic vaccine development.
3457 16987064 In the current study, a number of HLA-A*0201-restricted CTL epitopes derived from HCV were evaluated by examining the peptide-binding affinity for major histocompatibility complex (MHC) class I molecules, the stability of peptide-MHC complexes, killing activities of peptide-induced CTLs, and frequencies of intracellular interferon (IFN)-gamma-positive CD8+ T cells.
3458 16990779 A number of synthetic peptides derived from nonamer sequences of the WT1 protein were designed in which single amino-acid substitutions were introduced at HLA-A0201 major histocompatibility complex (MHC)-binding positions.
3459 16998881 Increased frequencies of CD8+ T lymphocytes recognizing wild-type p53-derived epitopes in peripheral blood correlate with presence of epitope loss tumor variants in patients with hepatocellular carcinoma.
3460 16998881 Circulating CD8+ T cells specific for WT p53(149-157) and WT p53(264-272) HLA-A*0201 restricted epitopes were directly identified in the peripheral blood by the use of peptide/HLA-A2.1 tetramers in 24 HCC patients.
3461 16998881 Cytotoxic T lymphocyte (CTL) activity after WT p53 peptide-specific stimulation was assessed by analysis of granzyme B and interferon-gamma mRNA transcription, using a quantitative real-time polymerase chain reaction assay.
3462 16998881 Tumor immunophenotyping was performed to evaluate the p53 status, the expression of major histocompatibility complex (MHC) and costimulatory molecules in freshly isolated tumor cells.
3463 16998881 HCC patients exhibited significantly higher frequencies of WT p53-specific memory CD8+ T cells and stronger WT p53-specific CTL activity, when compared with healthy controls.
3464 16998881 Increased frequencies of p53-specific CD8+ T cells and their activity correlated with selective HLA-A2 allele loss and reduced costimulatory molecule expression of tumor cells.
3465 16998881 Moreover, augmented numbers of p53-specific T cells coincided with high MHC class II expression in tumor cells but were inversely related to the T status of the tumor node metastasis staging system.
3466 16998881 Increased frequencies of CD8+ T lymphocytes recognizing wild-type p53-derived epitopes in peripheral blood correlate with presence of epitope loss tumor variants in patients with hepatocellular carcinoma.
3467 16998881 Circulating CD8+ T cells specific for WT p53(149-157) and WT p53(264-272) HLA-A*0201 restricted epitopes were directly identified in the peripheral blood by the use of peptide/HLA-A2.1 tetramers in 24 HCC patients.
3468 16998881 Cytotoxic T lymphocyte (CTL) activity after WT p53 peptide-specific stimulation was assessed by analysis of granzyme B and interferon-gamma mRNA transcription, using a quantitative real-time polymerase chain reaction assay.
3469 16998881 Tumor immunophenotyping was performed to evaluate the p53 status, the expression of major histocompatibility complex (MHC) and costimulatory molecules in freshly isolated tumor cells.
3470 16998881 HCC patients exhibited significantly higher frequencies of WT p53-specific memory CD8+ T cells and stronger WT p53-specific CTL activity, when compared with healthy controls.
3471 16998881 Increased frequencies of p53-specific CD8+ T cells and their activity correlated with selective HLA-A2 allele loss and reduced costimulatory molecule expression of tumor cells.
3472 16998881 Moreover, augmented numbers of p53-specific T cells coincided with high MHC class II expression in tumor cells but were inversely related to the T status of the tumor node metastasis staging system.
3473 16998881 Increased frequencies of CD8+ T lymphocytes recognizing wild-type p53-derived epitopes in peripheral blood correlate with presence of epitope loss tumor variants in patients with hepatocellular carcinoma.
3474 16998881 Circulating CD8+ T cells specific for WT p53(149-157) and WT p53(264-272) HLA-A*0201 restricted epitopes were directly identified in the peripheral blood by the use of peptide/HLA-A2.1 tetramers in 24 HCC patients.
3475 16998881 Cytotoxic T lymphocyte (CTL) activity after WT p53 peptide-specific stimulation was assessed by analysis of granzyme B and interferon-gamma mRNA transcription, using a quantitative real-time polymerase chain reaction assay.
3476 16998881 Tumor immunophenotyping was performed to evaluate the p53 status, the expression of major histocompatibility complex (MHC) and costimulatory molecules in freshly isolated tumor cells.
3477 16998881 HCC patients exhibited significantly higher frequencies of WT p53-specific memory CD8+ T cells and stronger WT p53-specific CTL activity, when compared with healthy controls.
3478 16998881 Increased frequencies of p53-specific CD8+ T cells and their activity correlated with selective HLA-A2 allele loss and reduced costimulatory molecule expression of tumor cells.
3479 16998881 Moreover, augmented numbers of p53-specific T cells coincided with high MHC class II expression in tumor cells but were inversely related to the T status of the tumor node metastasis staging system.
3480 17005303 DNA immunisation in HLA-A*0201 and HLA-A*0201/HLA-DR1 transgenic mice resulted in the recovery of humoral response against the carrier and enhanced levels of HIV-1 specific CD8(+) T lymphocyte activation.
3481 17015458 We have found that intranasal immunization with recombinant chlamydial protease-like activity factor (CPAF) induces CD4(+) T-cell- and gamma interferon (IFN-gamma)-dependent protective immunity against murine genital chlamydial infection, thus making CPAF a viable vaccine candidate for further characterization.
3482 17015458 Upon CPAF-plus-interleukin-12 (IL-12) vaccination, HLA-DR4 tg animals exhibited robust CPAF-specific IFN-gamma production and elevated titers of anti-CPAF total antibody and immunoglobulin G2a (IgG2a) and lower titers of IgG2b and IgG1 antibodies.
3483 17015458 HLA-DR4 tg and C57BL/6 mice vaccinated with CPAF plus IL-12 resolved the primary genital chlamydial infection significantly earlier than mock-immunized animals, whereas similarly vaccinated MHC class II-deficient mice displayed minimal antigen-specific immune responses and failed to resolve the infection even at 30 days postchallenge.
3484 17016692 Enhanced induction of dendritic cell maturation and HLA-A*0201-restricted CEA-specific CD8(+) CTL response by exosomes derived from IL-18 gene-modified CEA-positive tumor cells.
3485 17016692 We transfected carcinoembryonic antigen (CEA)-expressing tumor cells with a recombinant adenovirus encoding human IL-18 (AdhIL-18) and prepared the exosomes, Exo/IL-18, from IL-18 gene-modified tumor cells.
3486 17016692 We found that Exo/IL-18 naturally contain CEA and bioactive IL-18.
3487 17016692 Furthermore, Exo/IL-18-pulsed DC are quite potent to induce HLA-A*0201-restricted, CEA-specific CD8(+) CTL from the PBMC of HLA-A*0201 CEA(+) cancer patients in vitro.
3488 17016692 Enhanced induction of dendritic cell maturation and HLA-A*0201-restricted CEA-specific CD8(+) CTL response by exosomes derived from IL-18 gene-modified CEA-positive tumor cells.
3489 17016692 We transfected carcinoembryonic antigen (CEA)-expressing tumor cells with a recombinant adenovirus encoding human IL-18 (AdhIL-18) and prepared the exosomes, Exo/IL-18, from IL-18 gene-modified tumor cells.
3490 17016692 We found that Exo/IL-18 naturally contain CEA and bioactive IL-18.
3491 17016692 Furthermore, Exo/IL-18-pulsed DC are quite potent to induce HLA-A*0201-restricted, CEA-specific CD8(+) CTL from the PBMC of HLA-A*0201 CEA(+) cancer patients in vitro.
3492 17067310 In this study, the non-canonical tumour-associated peptide from MUC1, MUC1-8 (SAPDTRPA), was modified at the MHC anchor residues to SAPDFRPL (MUC1-8-5F8L) and showed enhanced binding to H-2Kb and improved immune responses.
3493 17073943 In this study, we showed that ovalbumin (OVA) protein-pulsed DC (DC(OVA))-derived EXO (EXO(OVA)) displayed MHC class I-OVA I peptide (pMHC I) complexes, CD11c, CD40, CD80, CCR7, DEC205, Toll-like receptor 4 (TLR4), TLR9, MyD88 and DC-SIGN molecules, but at a lower level than DC(OVA).
3494 17073943 EXO(OVA) can be taken up by DC through LFA-1/CD54 and C-type lectin/mannose (glucosamine)-rich C-type lectin receptor (CLR) interactions.
3495 17073943 Mature DC pulsed with EXO(OVA), which were referred to as mDC(EXO), expressed a higher level of pMHC I, MHC II, and costimulatory CD40, CD54 and CD80 than DC(OVA).
3496 17073943 In this study, we showed that ovalbumin (OVA) protein-pulsed DC (DC(OVA))-derived EXO (EXO(OVA)) displayed MHC class I-OVA I peptide (pMHC I) complexes, CD11c, CD40, CD80, CCR7, DEC205, Toll-like receptor 4 (TLR4), TLR9, MyD88 and DC-SIGN molecules, but at a lower level than DC(OVA).
3497 17073943 EXO(OVA) can be taken up by DC through LFA-1/CD54 and C-type lectin/mannose (glucosamine)-rich C-type lectin receptor (CLR) interactions.
3498 17073943 Mature DC pulsed with EXO(OVA), which were referred to as mDC(EXO), expressed a higher level of pMHC I, MHC II, and costimulatory CD40, CD54 and CD80 than DC(OVA).
3499 17076705 Antibody depletion experiments showed that antituberculosis protective responses in the lung were not diminished by removal of CD8(+), T-cell receptor gammadelta (TCR-gammadelta(+)) and NK1.1(+) T cells from vaccinated CD4(-/-) mice before challenge, implying that the observed recall and immune effector functions resulting from vaccination of CD4(-/-) mice with mc(2)6030 were attributable to a population of CD4(-) CD8(-) (double-negative) TCR-alphabeta(+), TCR-gammadelta(-), NK1.1(-) T cells.
3500 17076705 Enriched pulmonary double-negative T cells transcribed significantly more interferon-gamma and interleukin-2 mRNA than double-negative T cells from naive mice after a tuberculous challenge.
3501 17076705 These results confirmed previous findings on the potential for a subset of MHC class II-restricted T cells to develop and function without expression of CD4 and suggest novel vaccination strategies to assist in the control of tuberculosis in human immunodeficiency virus-infected humans who have chronic depletion of their CD4(+) T cells.
3502 17094178 Results are presented for p/MHC microarrays consisting of a dimeric MHC-immunoglobulin complex, K(b)-Ig, loaded with either a cognate or non-cognate peptide for binding CD8(+) T cells.
3503 17106278 We found 10 class I alleles present in more than 10% of the population: HLA-A*02, HLA-A*11, HLA-A*24, HLA-B*13, HLA-B*15, HLA-B*40, HLA-Cw*03, HLA-Cw*07, HLA-Cw*01, and HLA-Cw*06.
3504 17106278 Several class II alleles were found at high frequency (>or=10%): HLA-DRB3, HLA-DRB4, HLA-DRB5, HLA-DRB1*0701, HLA-DRB1*1501, HLA-DRB1*0401, HLA-DRB1*0901, HLA-DRB1*1201, HLA-DQB1*0601, HLA-DQB1*0301, HLA-DQB1*0201, HLA-DQB1*0501, and HLA-DQB*0303.
3505 17106278 The HLA-B*14 allele was only found in the HIV-1-seropositive group, and many 2-locus haplotypes were significantly overrepresented in this group: HLA-B*14/Cw*08, HLA-B*51/Cw*14, HLA-A*02/B*13, HLA-A*31/Cw*14, HLA-A*02/Cw*06, and the class II haplotype HLA-DRB1*1301/DQB1*0601.
3506 17106278 Alleles significantly increased in the HIV-1-seronegative controls were HLA-B*44, HLA-Cw*04, and HLA-DRB1*1402.
3507 17106278 Overrepresented 2-locus haplotypes in the control group were HLA-B*44/Cw*04, HLA-A*31/Cw*03, HLA-A*03/Cw*07, HLA-A*11/B*13, HLA-A*11/B*38, HLA-A*24/B*52, and HLA-A*11/Cw*01.
3508 17106278 We found 10 class I alleles present in more than 10% of the population: HLA-A*02, HLA-A*11, HLA-A*24, HLA-B*13, HLA-B*15, HLA-B*40, HLA-Cw*03, HLA-Cw*07, HLA-Cw*01, and HLA-Cw*06.
3509 17106278 Several class II alleles were found at high frequency (>or=10%): HLA-DRB3, HLA-DRB4, HLA-DRB5, HLA-DRB1*0701, HLA-DRB1*1501, HLA-DRB1*0401, HLA-DRB1*0901, HLA-DRB1*1201, HLA-DQB1*0601, HLA-DQB1*0301, HLA-DQB1*0201, HLA-DQB1*0501, and HLA-DQB*0303.
3510 17106278 The HLA-B*14 allele was only found in the HIV-1-seropositive group, and many 2-locus haplotypes were significantly overrepresented in this group: HLA-B*14/Cw*08, HLA-B*51/Cw*14, HLA-A*02/B*13, HLA-A*31/Cw*14, HLA-A*02/Cw*06, and the class II haplotype HLA-DRB1*1301/DQB1*0601.
3511 17106278 Alleles significantly increased in the HIV-1-seronegative controls were HLA-B*44, HLA-Cw*04, and HLA-DRB1*1402.
3512 17106278 Overrepresented 2-locus haplotypes in the control group were HLA-B*44/Cw*04, HLA-A*31/Cw*03, HLA-A*03/Cw*07, HLA-A*11/B*13, HLA-A*11/B*38, HLA-A*24/B*52, and HLA-A*11/Cw*01.
3513 17106278 We found 10 class I alleles present in more than 10% of the population: HLA-A*02, HLA-A*11, HLA-A*24, HLA-B*13, HLA-B*15, HLA-B*40, HLA-Cw*03, HLA-Cw*07, HLA-Cw*01, and HLA-Cw*06.
3514 17106278 Several class II alleles were found at high frequency (>or=10%): HLA-DRB3, HLA-DRB4, HLA-DRB5, HLA-DRB1*0701, HLA-DRB1*1501, HLA-DRB1*0401, HLA-DRB1*0901, HLA-DRB1*1201, HLA-DQB1*0601, HLA-DQB1*0301, HLA-DQB1*0201, HLA-DQB1*0501, and HLA-DQB*0303.
3515 17106278 The HLA-B*14 allele was only found in the HIV-1-seropositive group, and many 2-locus haplotypes were significantly overrepresented in this group: HLA-B*14/Cw*08, HLA-B*51/Cw*14, HLA-A*02/B*13, HLA-A*31/Cw*14, HLA-A*02/Cw*06, and the class II haplotype HLA-DRB1*1301/DQB1*0601.
3516 17106278 Alleles significantly increased in the HIV-1-seronegative controls were HLA-B*44, HLA-Cw*04, and HLA-DRB1*1402.
3517 17106278 Overrepresented 2-locus haplotypes in the control group were HLA-B*44/Cw*04, HLA-A*31/Cw*03, HLA-A*03/Cw*07, HLA-A*11/B*13, HLA-A*11/B*38, HLA-A*24/B*52, and HLA-A*11/Cw*01.
3518 17106649 Flow cytometric analyses showed that TGF-beta2 does not suppress the upregulation of MHC (major histocompatibility complex) class II molecules and the T cell stimulatory capacity of human DC that were stimulated with a strong cytokine cocktail containing tumor necrosis factor alpha (TNF-alpha), IL-1beta, IL-6 and prostaglandin E2 (PGE2).
3519 17106649 Although both mature and immature DC expressed comparable amounts of the TGF-beta receptor type II, Smad2 phosphorylation and subsequent upregulation of Smad7 was inhibited in mature DC, but not immature DC.
3520 17106649 However, further analysis revealed that mature DC alone are not sufficient to mediate full T cell activation in the presence of TGF-beta2, unless IL-12 is added to the DC/T-cell coculture.
3521 17106649 Finally, we demonstrate that MHC class II expression and IL-12 secretion by DC are not disturbed by TGF-beta2 after DC stimulation with a modified maturation cocktail containing the Toll-like receptor (TLR)-ligands Poly I:C or R848, TNF-alpha, IL-1beta and INF-gamma.
3522 17106649 Flow cytometric analyses showed that TGF-beta2 does not suppress the upregulation of MHC (major histocompatibility complex) class II molecules and the T cell stimulatory capacity of human DC that were stimulated with a strong cytokine cocktail containing tumor necrosis factor alpha (TNF-alpha), IL-1beta, IL-6 and prostaglandin E2 (PGE2).
3523 17106649 Although both mature and immature DC expressed comparable amounts of the TGF-beta receptor type II, Smad2 phosphorylation and subsequent upregulation of Smad7 was inhibited in mature DC, but not immature DC.
3524 17106649 However, further analysis revealed that mature DC alone are not sufficient to mediate full T cell activation in the presence of TGF-beta2, unless IL-12 is added to the DC/T-cell coculture.
3525 17106649 Finally, we demonstrate that MHC class II expression and IL-12 secretion by DC are not disturbed by TGF-beta2 after DC stimulation with a modified maturation cocktail containing the Toll-like receptor (TLR)-ligands Poly I:C or R848, TNF-alpha, IL-1beta and INF-gamma.
3526 17116173 Our results support the concept that MHC class II-positive/Ii-negative (class II(+)/Ii(-)) antigen-presenting cells (APC) present endogenously synthesized vaccine antigens simultaneously by MHC class II and class I molecules, activating both CD4(+) and CD8(+) T cells.
3527 17116173 Activated CD4(+) T cells locally strengthen the response of CD8(+) CTL, thus enhancing the potency of a DNA vaccine.
3528 17116980 Cytotoxicity was mainly mediated by CD8+ T cells in a HLA class I-restricted manner.
3529 17119951 The modular concept increased the number of predictable alleles from 15 to 75 of HLA-A and 12 to 36 of HLA-B proteins.
3530 17121795 In this study, we have established that a vaccine platform based on the coat protein of papaya mosaic virus (PapMV CP), previously shown to induce a humoral response, can induce major histocompatibility complex (MHC) class I cross-presentation of HLA-A*0201 epitopes from gp100, a melanoma antigen, and from influenza virus M1 matrix protein.
3531 17121795 When we pulsed HLA-A*0201+ antigen-presenting cells (APCs) with the recombinant PapMV FLU or gp100, we noted that antigen-specific CD8+ T cells were highly reactive to these APCs, demonstrating that the epitope from the VLPs were processed and loaded on the MHC class I complex.
3532 17121795 In this study, we have established that a vaccine platform based on the coat protein of papaya mosaic virus (PapMV CP), previously shown to induce a humoral response, can induce major histocompatibility complex (MHC) class I cross-presentation of HLA-A*0201 epitopes from gp100, a melanoma antigen, and from influenza virus M1 matrix protein.
3533 17121795 When we pulsed HLA-A*0201+ antigen-presenting cells (APCs) with the recombinant PapMV FLU or gp100, we noted that antigen-specific CD8+ T cells were highly reactive to these APCs, demonstrating that the epitope from the VLPs were processed and loaded on the MHC class I complex.
3534 17130554 In the non-obese diabetic (NOD) mouse model, CD8+ T cells play an essential role in both the initial triggering of insulitis and its destructive phase, and proinsulin (PI) is one of the dominant target antigens (Ags).
3535 17130554 However, little is known about the beta cell epitopes presented by HLA class I molecules and recognized by human CD8+ T cells.
3536 17130554 We validated immunogenicity and natural processing of the identified PI epitopes in HLA-A2.1-transgenic mice, while others demonstrated recognition of multiple PI epitopes by CD8+ T cells from T1DM and healthy subjects in the context of different HLA class I molecules.
3537 17130554 DNA vaccination of HLA-transgenic mice may be another rapid and efficient reverse immunology approach to map additional epitopes derived from other T1DM Ags, such as IA-2 and glutamic acid decarboxylase 65 (GAD 65).
3538 17130554 Transfer of this information to Elispot- and MHC tetramer-based assay formats should allow to reliably detect and characterize autoreactive CD8+ T cell responses in T1DM, and may open new avenues for early T1DM diagnosis and immune intervention.
3539 17130554 In the non-obese diabetic (NOD) mouse model, CD8+ T cells play an essential role in both the initial triggering of insulitis and its destructive phase, and proinsulin (PI) is one of the dominant target antigens (Ags).
3540 17130554 However, little is known about the beta cell epitopes presented by HLA class I molecules and recognized by human CD8+ T cells.
3541 17130554 We validated immunogenicity and natural processing of the identified PI epitopes in HLA-A2.1-transgenic mice, while others demonstrated recognition of multiple PI epitopes by CD8+ T cells from T1DM and healthy subjects in the context of different HLA class I molecules.
3542 17130554 DNA vaccination of HLA-transgenic mice may be another rapid and efficient reverse immunology approach to map additional epitopes derived from other T1DM Ags, such as IA-2 and glutamic acid decarboxylase 65 (GAD 65).
3543 17130554 Transfer of this information to Elispot- and MHC tetramer-based assay formats should allow to reliably detect and characterize autoreactive CD8+ T cell responses in T1DM, and may open new avenues for early T1DM diagnosis and immune intervention.
3544 17130554 In the non-obese diabetic (NOD) mouse model, CD8+ T cells play an essential role in both the initial triggering of insulitis and its destructive phase, and proinsulin (PI) is one of the dominant target antigens (Ags).
3545 17130554 However, little is known about the beta cell epitopes presented by HLA class I molecules and recognized by human CD8+ T cells.
3546 17130554 We validated immunogenicity and natural processing of the identified PI epitopes in HLA-A2.1-transgenic mice, while others demonstrated recognition of multiple PI epitopes by CD8+ T cells from T1DM and healthy subjects in the context of different HLA class I molecules.
3547 17130554 DNA vaccination of HLA-transgenic mice may be another rapid and efficient reverse immunology approach to map additional epitopes derived from other T1DM Ags, such as IA-2 and glutamic acid decarboxylase 65 (GAD 65).
3548 17130554 Transfer of this information to Elispot- and MHC tetramer-based assay formats should allow to reliably detect and characterize autoreactive CD8+ T cell responses in T1DM, and may open new avenues for early T1DM diagnosis and immune intervention.
3549 17157489 Cross-presentation of exogenous proteins on MHC class I complexes contributes to the priming CD8(+) T-cell responses.
3550 17162382 The relative risks of HLA class I genotypes for Rasmussen syndrome are 6.1 (A*2402), 6.4 (A*0201), 6.3 (A*2601) and 11.4 (B*4601).
3551 17166907 We identified four HLA-A*0201-restricted peptides-nucleoprotein NP(69-77), glycoprotein precursor GPC(10-18), GPC(447-455), and zinc-binding protein Z(49-58)-that displayed high-affinity binding (< or =275 nM) to HLA-A*0201, induced CD8(+) T-cell responses of high functional avidity in HLA-A*0201 transgenic mice, and were naturally processed from native LCMV antigens in HLA-restricted human antigen presenting cells.
3552 17166907 One of the epitopes (GPC(447-455)), after peptide immunization of HLA-A*0201 mice, induced CD8(+) T cells capable of killing peptide-pulsed HLA-A*0201-restricted target cells in vivo and protected mice against lethal intracranial challenge with LCMV.
3553 17166907 We identified four HLA-A*0201-restricted peptides-nucleoprotein NP(69-77), glycoprotein precursor GPC(10-18), GPC(447-455), and zinc-binding protein Z(49-58)-that displayed high-affinity binding (< or =275 nM) to HLA-A*0201, induced CD8(+) T-cell responses of high functional avidity in HLA-A*0201 transgenic mice, and were naturally processed from native LCMV antigens in HLA-restricted human antigen presenting cells.
3554 17166907 One of the epitopes (GPC(447-455)), after peptide immunization of HLA-A*0201 mice, induced CD8(+) T cells capable of killing peptide-pulsed HLA-A*0201-restricted target cells in vivo and protected mice against lethal intracranial challenge with LCMV.
3555 17182178 Identification of an HLA-A*0201 restricted Bcl2-derived epitope expressed on tumors.
3556 17182178 An HLA-A*0201 restricted CTL epitope was deduced in silica from the amino acid sequence of the Bcl2 protein and its binding affinity for HLA-A*0201 was confirmed using a biochemical binding assay.
3557 17182178 These Bcl2(85-93) specific CTLs react with and lyse Bcl2-expressing human colon carcinoma CCL220 cells which have been transfected with a chimeric HLA-A*0201/H2-K(b) DNA construct similar to that expressed in the transgenic mice.
3558 17182178 Identification of an HLA-A*0201 restricted Bcl2-derived epitope expressed on tumors.
3559 17182178 An HLA-A*0201 restricted CTL epitope was deduced in silica from the amino acid sequence of the Bcl2 protein and its binding affinity for HLA-A*0201 was confirmed using a biochemical binding assay.
3560 17182178 These Bcl2(85-93) specific CTLs react with and lyse Bcl2-expressing human colon carcinoma CCL220 cells which have been transfected with a chimeric HLA-A*0201/H2-K(b) DNA construct similar to that expressed in the transgenic mice.
3561 17182178 Identification of an HLA-A*0201 restricted Bcl2-derived epitope expressed on tumors.
3562 17182178 An HLA-A*0201 restricted CTL epitope was deduced in silica from the amino acid sequence of the Bcl2 protein and its binding affinity for HLA-A*0201 was confirmed using a biochemical binding assay.
3563 17182178 These Bcl2(85-93) specific CTLs react with and lyse Bcl2-expressing human colon carcinoma CCL220 cells which have been transfected with a chimeric HLA-A*0201/H2-K(b) DNA construct similar to that expressed in the transgenic mice.
3564 17182686 The importance of HLA class I-restricted CD8 T-cell responses in the control of human immunodeficiency virus (HIV) infection is generally accepted.
3565 17182686 While several studies have shown an association of certain HLA class I alleles with slower disease progression, it is not fully established whether this effect is mediated by HIV-specific CD8 T-cell responses restricted by these alleles.
3566 17182686 In order to study the influence of the HLA class I alleles on the HIV-specific CD8 T-cell response and on viral control, we have assessed HIV-specific epitope recognition, plasma viral load, and expression of HLA class I alleles in a cohort of HIV-seropositive bar workers.
3567 17182686 The importance of HLA class I-restricted CD8 T-cell responses in the control of human immunodeficiency virus (HIV) infection is generally accepted.
3568 17182686 While several studies have shown an association of certain HLA class I alleles with slower disease progression, it is not fully established whether this effect is mediated by HIV-specific CD8 T-cell responses restricted by these alleles.
3569 17182686 In order to study the influence of the HLA class I alleles on the HIV-specific CD8 T-cell response and on viral control, we have assessed HIV-specific epitope recognition, plasma viral load, and expression of HLA class I alleles in a cohort of HIV-seropositive bar workers.
3570 17182686 The importance of HLA class I-restricted CD8 T-cell responses in the control of human immunodeficiency virus (HIV) infection is generally accepted.
3571 17182686 While several studies have shown an association of certain HLA class I alleles with slower disease progression, it is not fully established whether this effect is mediated by HIV-specific CD8 T-cell responses restricted by these alleles.
3572 17182686 In order to study the influence of the HLA class I alleles on the HIV-specific CD8 T-cell response and on viral control, we have assessed HIV-specific epitope recognition, plasma viral load, and expression of HLA class I alleles in a cohort of HIV-seropositive bar workers.
3573 17198083 DC pulsed with P. carinii did not demonstrate increased expression of the cell surface markers MHC II, CD40, CD54, CD80 (B7.1), and CD86 (B7.2).
3574 17198083 The release of interleukin (IL)-4 was increased, but there was no increase in the release of interleukin (IL)-12p40, IL-10, tumor necrosis factor-alpha, IL-6, and nitrite compared with naive DC.
3575 17198083 In vivo administration of DC pulsed with P. carinii induced a P. carinii-specific response, generating CD4+ cells that proliferated and released IL-4, but not interferon-gamma, in response to P. carinii-pulsed DC in vitro.
3576 17202219 To determine the influence of human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T cells on the development of drug resistance mutations in the HIV-1 protease, we analyzed protease sequences from viruses from a human leukocyte antigen class I (HLA class I)-typed cohort of 94 HIV-1-positive individuals.
3577 17202219 A subset of these observed correlations was experimentally validated by enzyme-linked immunospot assays, allowing the definition of 10 new epitopes recognized by CD8+ T cells from patients with the appropriate HLA class I type.
3578 17202219 To determine the influence of human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T cells on the development of drug resistance mutations in the HIV-1 protease, we analyzed protease sequences from viruses from a human leukocyte antigen class I (HLA class I)-typed cohort of 94 HIV-1-positive individuals.
3579 17202219 A subset of these observed correlations was experimentally validated by enzyme-linked immunospot assays, allowing the definition of 10 new epitopes recognized by CD8+ T cells from patients with the appropriate HLA class I type.
3580 17204851 In these antigen presenting cells, autophagosomes frequently fused with MHC class II antigen loading compartments and targeting of Influenza matrix protein 1 (MP1) for macroautophagy enhanced MHC class II presentation to MP1-specific CD4+ T cell clones up to 20 fold.
3581 17204851 We suggest that this pathway samples intracellular proteins for immune surveillance and induction of tolerance in CD4+ T cells, and could be targeted for improved MHC class II presentation of vaccine antigens.
3582 17204851 In these antigen presenting cells, autophagosomes frequently fused with MHC class II antigen loading compartments and targeting of Influenza matrix protein 1 (MP1) for macroautophagy enhanced MHC class II presentation to MP1-specific CD4+ T cell clones up to 20 fold.
3583 17204851 We suggest that this pathway samples intracellular proteins for immune surveillance and induction of tolerance in CD4+ T cells, and could be targeted for improved MHC class II presentation of vaccine antigens.
3584 17205139 Previous studies of HIV-1 p55Gag immunization of mice have demonstrated the usefulness of targeting antigens to the cellular compartment containing the major histocompatibility complex type II (MHC II) complex molecules by use of a DNA antigen formulation encoding Gag as a chimera with the mouse lysosome-associated membrane protein (mLAMP/gag).
3585 17205139 ELISPOT analyses indicated that the average Gag-specific IFN-gamma response elicited by the hLAMP/gag chimera was detectable after only two or three naked DNA immunizations in all five immunized macaques and reached an average of 1000 spot-forming cells (SFC)/10(6) PBMCs.
3586 17205139 High IFN-gamma ELISPOT responses were detected in CD8(+)-depleted cells, indicating that CD4(+) T-cells play a major role in these responses.
3587 17215337 We studied the association between HLA alleles and rubella-specific gamma interferon (IFN-gamma) (Th1) and interleukin-10 (IL-10) (Th2) cytokine responses among 106 healthy children (ages, 14 to 17 years) previously immunized with two doses of rubella vaccine.
3588 17215337 Several class I HLA-A (*0201, *2402, *6801) alleles were significantly associated with rubella vaccine-induced IFN-gamma secretion.
3589 17215337 Several class II HLA-DRB1 (*0101) and HLA-DQB1 (*0501) alleles were also suggestive of an association with IFN-gamma secretion.
3590 17215337 Alleles with potential associations with rubella-specific IL-10 production included HLA-A (*0201, *6801), HLA-B (*4901), and HLA-DRB1 (*1302).
3591 17215337 The class I A*0201 and A*6801 alleles were associated with both IFN-gamma and IL-10 secretion.
3592 17215337 We studied the association between HLA alleles and rubella-specific gamma interferon (IFN-gamma) (Th1) and interleukin-10 (IL-10) (Th2) cytokine responses among 106 healthy children (ages, 14 to 17 years) previously immunized with two doses of rubella vaccine.
3593 17215337 Several class I HLA-A (*0201, *2402, *6801) alleles were significantly associated with rubella vaccine-induced IFN-gamma secretion.
3594 17215337 Several class II HLA-DRB1 (*0101) and HLA-DQB1 (*0501) alleles were also suggestive of an association with IFN-gamma secretion.
3595 17215337 Alleles with potential associations with rubella-specific IL-10 production included HLA-A (*0201, *6801), HLA-B (*4901), and HLA-DRB1 (*1302).
3596 17215337 The class I A*0201 and A*6801 alleles were associated with both IFN-gamma and IL-10 secretion.
3597 17219364 FACS analysis demonstrated an up-regulation of DC maturation markers CD80, CD86, CD40 and MHC class II upon exposure to Gal-lectin.
3598 17219364 The activation of DC by Gal-lectin was mediated by MAPK and NF-kappaB.
3599 17225159 Most of the predicted peptides exhibited strong binding to the HLA-A*2402 molecule, while also inducing CD8 T cell responses from the patients' peripheral blood mononuclear cells (PBMCs).
3600 17229838 DEC-205 receptor on dendritic cells mediates presentation of HIV gag protein to CD8+ T cells in a spectrum of human MHC I haplotypes.
3601 17229838 Optimal HIV vaccines should elicit CD8+ T cells specific for HIV proteins presented on MHC class I products, because these T cells contribute to host resistance to viruses.
3602 17229838 To extend this finding to humans, we introduced the HIV p24 gag protein into a mAb that targets DEC-205/CD205, an endocytic receptor of DCs.
3603 17229838 We then assessed cross-presentation, which is the processing of nonreplicating internalized antigen onto MHC class I for recognition by CD8+ T cells.
3604 17229838 Low doses of alphaDEC-gag, but not control Ig-gag, stimulated proliferation and IFN-gamma production by CD8+ T cells isolated from the blood of HIV-infected donors. alphaCD205 fusion mAb was more effective for cross-presentation than alphaCD209/DC-SIGN, another abundant DC uptake receptor.
3605 17229838 Our results, based on humans with highly polymorphic MHC products, reveal that DCs and DEC-205 can cross-present several different peptides from a single protein.
3606 17229838 DEC-205 receptor on dendritic cells mediates presentation of HIV gag protein to CD8+ T cells in a spectrum of human MHC I haplotypes.
3607 17229838 Optimal HIV vaccines should elicit CD8+ T cells specific for HIV proteins presented on MHC class I products, because these T cells contribute to host resistance to viruses.
3608 17229838 To extend this finding to humans, we introduced the HIV p24 gag protein into a mAb that targets DEC-205/CD205, an endocytic receptor of DCs.
3609 17229838 We then assessed cross-presentation, which is the processing of nonreplicating internalized antigen onto MHC class I for recognition by CD8+ T cells.
3610 17229838 Low doses of alphaDEC-gag, but not control Ig-gag, stimulated proliferation and IFN-gamma production by CD8+ T cells isolated from the blood of HIV-infected donors. alphaCD205 fusion mAb was more effective for cross-presentation than alphaCD209/DC-SIGN, another abundant DC uptake receptor.
3611 17229838 Our results, based on humans with highly polymorphic MHC products, reveal that DCs and DEC-205 can cross-present several different peptides from a single protein.
3612 17229838 DEC-205 receptor on dendritic cells mediates presentation of HIV gag protein to CD8+ T cells in a spectrum of human MHC I haplotypes.
3613 17229838 Optimal HIV vaccines should elicit CD8+ T cells specific for HIV proteins presented on MHC class I products, because these T cells contribute to host resistance to viruses.
3614 17229838 To extend this finding to humans, we introduced the HIV p24 gag protein into a mAb that targets DEC-205/CD205, an endocytic receptor of DCs.
3615 17229838 We then assessed cross-presentation, which is the processing of nonreplicating internalized antigen onto MHC class I for recognition by CD8+ T cells.
3616 17229838 Low doses of alphaDEC-gag, but not control Ig-gag, stimulated proliferation and IFN-gamma production by CD8+ T cells isolated from the blood of HIV-infected donors. alphaCD205 fusion mAb was more effective for cross-presentation than alphaCD209/DC-SIGN, another abundant DC uptake receptor.
3617 17229838 Our results, based on humans with highly polymorphic MHC products, reveal that DCs and DEC-205 can cross-present several different peptides from a single protein.
3618 17229838 DEC-205 receptor on dendritic cells mediates presentation of HIV gag protein to CD8+ T cells in a spectrum of human MHC I haplotypes.
3619 17229838 Optimal HIV vaccines should elicit CD8+ T cells specific for HIV proteins presented on MHC class I products, because these T cells contribute to host resistance to viruses.
3620 17229838 To extend this finding to humans, we introduced the HIV p24 gag protein into a mAb that targets DEC-205/CD205, an endocytic receptor of DCs.
3621 17229838 We then assessed cross-presentation, which is the processing of nonreplicating internalized antigen onto MHC class I for recognition by CD8+ T cells.
3622 17229838 Low doses of alphaDEC-gag, but not control Ig-gag, stimulated proliferation and IFN-gamma production by CD8+ T cells isolated from the blood of HIV-infected donors. alphaCD205 fusion mAb was more effective for cross-presentation than alphaCD209/DC-SIGN, another abundant DC uptake receptor.
3623 17229838 Our results, based on humans with highly polymorphic MHC products, reveal that DCs and DEC-205 can cross-present several different peptides from a single protein.
3624 17238276 For instance, the K5 modulator of immune recognition (MIR2) from Kaposi sarcoma-associated herpesvirus prevents activation of cytotoxic T cells, natural killer cells, and natural killer T cells by downregulating major histocompatibility complex (MHC) class I molecules, the MHC-like molecule CD1, the cell adhesion molecules ICAM-1 and PECAM, and the co-stimulatory molecule B7.2.
3625 17238276 Mass spectrometric protein identification revealed four proteins that were consistently underrepresented in the plasma membrane of K5 expression cells: MHC I (as expected), bone marrow stromal antigen 2 (BST-2, CD316), activated leukocyte cell adhesion molecule (ALCAM, CD166) and Syntaxin-4.
3626 17238276 Since ALCAM is the ligand for CD6, a member of the immunological synapse of T cells, its removal by viral immune modulators implies a role for CD6 in the recognition of pathogens by T cells.
3627 17238276 For instance, the K5 modulator of immune recognition (MIR2) from Kaposi sarcoma-associated herpesvirus prevents activation of cytotoxic T cells, natural killer cells, and natural killer T cells by downregulating major histocompatibility complex (MHC) class I molecules, the MHC-like molecule CD1, the cell adhesion molecules ICAM-1 and PECAM, and the co-stimulatory molecule B7.2.
3628 17238276 Mass spectrometric protein identification revealed four proteins that were consistently underrepresented in the plasma membrane of K5 expression cells: MHC I (as expected), bone marrow stromal antigen 2 (BST-2, CD316), activated leukocyte cell adhesion molecule (ALCAM, CD166) and Syntaxin-4.
3629 17238276 Since ALCAM is the ligand for CD6, a member of the immunological synapse of T cells, its removal by viral immune modulators implies a role for CD6 in the recognition of pathogens by T cells.
3630 17263647 HLA-B alleles were involved in more associations (50%) than alleles from either the HLA-A (27%) or HLA-C (24%) loci.
3631 17275522 DC were propagated from C3H (H2(k)) bone marrow (BM) using granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4).
3632 17275522 Expression of major histocompatibility complex (MHC) class I and II was not affected, while CD40, CD80, and CD86 costimulatory molecules on DC were significantly inhibited by treatment with TGF-beta.
3633 17275522 This observation correlated with reduced interferon-gamma (IFN-gamma) and increased IL-10 production.
3634 17277122 Human immature dendritic cells (DCs) cultured in the presence of c-di-GMP showed increased expression of costimulatory molecules CD80/CD86 and maturation marker CD83, increased MHC class II and cytokines and chemokines such as IL-12, IFN-gamma, IL-8, MCP-1, IFN-gamma-inducible protein 10, and RANTES, and altered expression of chemokine receptors including CCR1, CCR7, and CXCR4. c-di-GMP-matured DCs demonstrated enhanced T cell stimulatory activity. c-di-GMP activated p38 MAPK in human DCs and ERK phosphorylation in human macrophages. c-di-GMP is stable in human serum.
3635 17283103 Detection of antigen-specific CD4+ T cells is facilitated by the use of fluorescently labeled soluble peptide-major histocompatibility complex (MHC) multimers which mirror the antigen specificity of T-cell receptor recognition.
3636 17293384 Targeting HER-2/neu in early breast cancer development using dendritic cells with staged interleukin-12 burst secretion.
3637 17293384 Before surgical resection, HER-2/neu(pos) DCIS patients (n = 13) received 4 weekly vaccinations of dendritic cells pulsed with HER-2/neu HLA class I and II peptides.
3638 17293384 Before vaccination, many subjects possessed HER-2/neu-HLA-A2 tetramer-staining CD8(pos) T cells that expressed low levels of CD28 and high levels of the inhibitory B7 ligand CTLA-4, but this ratio inverted after vaccination.
3639 17293384 The vaccinated subjects also showed high rates of peptide-specific sensitization for both IFN-gamma-secreting CD4(pos) (85%) and CD8(pos) (80%) T cells, with recognition of antigenically relevant breast cancer lines, accumulation of T and B lymphocytes in the breast, and induction of complement-dependent, tumor-lytic antibodies.
3640 17294448 Immunological characterization of missense mutations occurring within cytotoxic T cell-defined p53 epitopes in HLA-A*0201+ squamous cell carcinomas of the head and neck.
3641 17294448 Previous analyses of p53 in 40 HLA-A*0201(HLA-A2)(+) squamous cell carcinomas of the head and neck (SCCHN) indicated that 6/13 p53 missense mutations that were detected, S149C, T150R, V157F, Y220C, Y220H and E271K, occurred within HLA-A2-restricted cytotoxic T lymphocyte (CTL)-defined p53 epitopes.
3642 17294448 These results indicate that the p53 Y220C mutation can be processed and presented for CD8(+) T cell recognition.
3643 17294448 In contrast, independent of their HLA class I genotypes, the p53 Y220C mutation frequency for all human tumors analyzed to date is approximately 1.5%.
3644 17294448 Immunological characterization of missense mutations occurring within cytotoxic T cell-defined p53 epitopes in HLA-A*0201+ squamous cell carcinomas of the head and neck.
3645 17294448 Previous analyses of p53 in 40 HLA-A*0201(HLA-A2)(+) squamous cell carcinomas of the head and neck (SCCHN) indicated that 6/13 p53 missense mutations that were detected, S149C, T150R, V157F, Y220C, Y220H and E271K, occurred within HLA-A2-restricted cytotoxic T lymphocyte (CTL)-defined p53 epitopes.
3646 17294448 These results indicate that the p53 Y220C mutation can be processed and presented for CD8(+) T cell recognition.
3647 17294448 In contrast, independent of their HLA class I genotypes, the p53 Y220C mutation frequency for all human tumors analyzed to date is approximately 1.5%.
3648 17294448 Immunological characterization of missense mutations occurring within cytotoxic T cell-defined p53 epitopes in HLA-A*0201+ squamous cell carcinomas of the head and neck.
3649 17294448 Previous analyses of p53 in 40 HLA-A*0201(HLA-A2)(+) squamous cell carcinomas of the head and neck (SCCHN) indicated that 6/13 p53 missense mutations that were detected, S149C, T150R, V157F, Y220C, Y220H and E271K, occurred within HLA-A2-restricted cytotoxic T lymphocyte (CTL)-defined p53 epitopes.
3650 17294448 These results indicate that the p53 Y220C mutation can be processed and presented for CD8(+) T cell recognition.
3651 17294448 In contrast, independent of their HLA class I genotypes, the p53 Y220C mutation frequency for all human tumors analyzed to date is approximately 1.5%.
3652 17302734 The liposomes did not have an effect on the maturation of murine bone-marrow-derived dendritic cells (BM-DCs) related to the surface expression of major histocompatibility complex (MHC) class II, CD40, CD80 and CD86.
3653 17306360 These should be directed at the level of gene selection and delivery, in order to identify the optimal cytokine and achieve efficient and durable cytokine expression, and at the level of improving immune stimulation, i.e. by co-administration of co-stimulatory molecules including B7 and CD40, or boosting the expression of tumor antigens or MHC class I molecules.
3654 17306360 Interestingly, some of the cytokines which have shown encouraging anti-tumor activity, including IFNs, IL-4, IL-12 and TNF-alpha, are endowed with anti-angiogenic or vasculotoxic effects, which may significantly contribute to local tumor control.
3655 17339435 Preferential usage of specific TCRs and the in vitro functional TCR-alpha- and -beta-chain-pairing assay suggests that every peptide/MHC complex may only be recognized by a limited number of unique combinations of alpha- and beta-chain pairs.
3656 17367207 However, the capsular polysaccharide Sp1 from Streptococcus pneumoniae serotype 1 has been shown to activate CD4(+) T cells in a major histocompatibility complex (MHC) class II-dependent manner.
3657 17371975 Human dendritic cells acquire a semimature phenotype and lymph node homing potential through interaction with CD4+CD25+ regulatory T cells.
3658 17371975 The results showed that interaction with CD25(high)CD4+ regulatory T cells (Tregs) caused DC to take on very different properties than contact with naive or memory phenotype T cells.
3659 17371975 However, DC exposed to Tregs also showed some changes typically associated with DC maturation, namely, increased expression of CCR7 and MHC class II molecules, and gained the ability to migrate in response to the CCR7 ligand CCL19.
3660 17387166 Two new T-cell epitopes were identified, p91-105 and p31-50, restricted via HLA-A*0201 and HLA-DRB1*0301, respectively.
3661 17429413 Impact of MHC class I alleles on the M. tuberculosis antigen-specific CD8+ T-cell response in patients with pulmonary tuberculosis.
3662 17429413 Affinity (ED(50)) and half-life (t(1/2), off-rate) analysis for individual peptide species on HLA-A and HLA-B molecules revealed binding ranges between 10(-3) and 10(-7) M.
3663 17429413 Peptides that bound with slow off-rates to class I alleles, that is HLA-A*0201, were associated with low frequency of CD8+ T cells in PBMCs from patients with tuberculosis.
3664 17429413 HLA-B alleles showed fast off-rates in peptide binding and restricted high numbers (up to 6%) of antigen-specific CD8+ T cells in patients with pulmonary tuberculosis.
3665 17429413 Impact of MHC class I alleles on the M. tuberculosis antigen-specific CD8+ T-cell response in patients with pulmonary tuberculosis.
3666 17429413 Affinity (ED(50)) and half-life (t(1/2), off-rate) analysis for individual peptide species on HLA-A and HLA-B molecules revealed binding ranges between 10(-3) and 10(-7) M.
3667 17429413 Peptides that bound with slow off-rates to class I alleles, that is HLA-A*0201, were associated with low frequency of CD8+ T cells in PBMCs from patients with tuberculosis.
3668 17429413 HLA-B alleles showed fast off-rates in peptide binding and restricted high numbers (up to 6%) of antigen-specific CD8+ T cells in patients with pulmonary tuberculosis.
3669 17429413 Impact of MHC class I alleles on the M. tuberculosis antigen-specific CD8+ T-cell response in patients with pulmonary tuberculosis.
3670 17429413 Affinity (ED(50)) and half-life (t(1/2), off-rate) analysis for individual peptide species on HLA-A and HLA-B molecules revealed binding ranges between 10(-3) and 10(-7) M.
3671 17429413 Peptides that bound with slow off-rates to class I alleles, that is HLA-A*0201, were associated with low frequency of CD8+ T cells in PBMCs from patients with tuberculosis.
3672 17429413 HLA-B alleles showed fast off-rates in peptide binding and restricted high numbers (up to 6%) of antigen-specific CD8+ T cells in patients with pulmonary tuberculosis.
3673 17430097 Development of naturally occurring CD4+CD25+ T regulatory cells (Treg) in the thymus requires the transcription factor Foxp3.
3674 17430097 Major histocompatibility complex (MHC) class II, self-ligands expressed by epithelial cells, and thymic stromal lymphopoietin also appear to play important roles.
3675 17442958 Different evolutionary histories of the two classical class I genes BF1 and BF2 illustrate drift and selection within the stable MHC haplotypes of chickens.
3676 17442958 First, six other haplotypes have the same genomic organization as B12, with a poorly expressed (minor) BF1 gene between DMB2 and TAP2 and a well-expressed (major) BF2 gene between TAP2 and C4.
3677 17447064 The HLA-A*0201-binding CEA(694-702) peptide was recently isolated from acid eluted MHC-I associated peptides from a human colon tumor cell line.
3678 17447064 We found that the peptide CEA(694-702) binds weakly to HLA-A*0201 molecules and is ineffective at inducing specific CD8+ T-cell responses in healthy donors.
3679 17447064 Tumor cells expressing CEA were recognized in a peptide and HLA-A*0201 restricted fashion, but high-CEA expression levels appear to be required for CTL recognition.
3680 17447064 However, the CEA-specific CD8+ T-cell clones derived from cancer patients revealed low-functional avidity and impaired tumor-cell recognition.
3681 17447064 The HLA-A*0201-binding CEA(694-702) peptide was recently isolated from acid eluted MHC-I associated peptides from a human colon tumor cell line.
3682 17447064 We found that the peptide CEA(694-702) binds weakly to HLA-A*0201 molecules and is ineffective at inducing specific CD8+ T-cell responses in healthy donors.
3683 17447064 Tumor cells expressing CEA were recognized in a peptide and HLA-A*0201 restricted fashion, but high-CEA expression levels appear to be required for CTL recognition.
3684 17447064 However, the CEA-specific CD8+ T-cell clones derived from cancer patients revealed low-functional avidity and impaired tumor-cell recognition.
3685 17447064 The HLA-A*0201-binding CEA(694-702) peptide was recently isolated from acid eluted MHC-I associated peptides from a human colon tumor cell line.
3686 17447064 We found that the peptide CEA(694-702) binds weakly to HLA-A*0201 molecules and is ineffective at inducing specific CD8+ T-cell responses in healthy donors.
3687 17447064 Tumor cells expressing CEA were recognized in a peptide and HLA-A*0201 restricted fashion, but high-CEA expression levels appear to be required for CTL recognition.
3688 17447064 However, the CEA-specific CD8+ T-cell clones derived from cancer patients revealed low-functional avidity and impaired tumor-cell recognition.
3689 17464507 By the use of a neural network capable of performing quantitative predictions of peptides binding to HLA-A*0201 molecules, we identified a number of nonamer peptides derived from the catalytic subunit of telomerase, human telomerase reverse transcriptase (hTERT).
3690 17464507 In order to show reactivity against naturally processed peptide in human tumor cells, an hTERT positive HLA-A*0201 negative colon carcinoma cell line (CCL220) was transfected with an HLA-A*0201/H2K(b) cDNA construct and used as target in ELISPOT and cytotoxicity assays.
3691 17464507 In conclusion, we have identified a new CTL HLA-A*0201 restricted hTERT epitope, which is now, included in an ongoing phase 2 vaccine trial of patients with disseminated cancer.
3692 17464507 By the use of a neural network capable of performing quantitative predictions of peptides binding to HLA-A*0201 molecules, we identified a number of nonamer peptides derived from the catalytic subunit of telomerase, human telomerase reverse transcriptase (hTERT).
3693 17464507 In order to show reactivity against naturally processed peptide in human tumor cells, an hTERT positive HLA-A*0201 negative colon carcinoma cell line (CCL220) was transfected with an HLA-A*0201/H2K(b) cDNA construct and used as target in ELISPOT and cytotoxicity assays.
3694 17464507 In conclusion, we have identified a new CTL HLA-A*0201 restricted hTERT epitope, which is now, included in an ongoing phase 2 vaccine trial of patients with disseminated cancer.
3695 17464507 By the use of a neural network capable of performing quantitative predictions of peptides binding to HLA-A*0201 molecules, we identified a number of nonamer peptides derived from the catalytic subunit of telomerase, human telomerase reverse transcriptase (hTERT).
3696 17464507 In order to show reactivity against naturally processed peptide in human tumor cells, an hTERT positive HLA-A*0201 negative colon carcinoma cell line (CCL220) was transfected with an HLA-A*0201/H2K(b) cDNA construct and used as target in ELISPOT and cytotoxicity assays.
3697 17464507 In conclusion, we have identified a new CTL HLA-A*0201 restricted hTERT epitope, which is now, included in an ongoing phase 2 vaccine trial of patients with disseminated cancer.
3698 17467840 Maturation markers (CD80, CD86, MHC Class II molecules) showed significantly enhanced expression on DC pulsed with high density R8-modified liposomes containing mycobacterial CW.
3699 17467840 Moreover, R8-modified liposomes with mycobacterial CW incorporated induced production of IL-12 p40 by DC, at levels similar to those produced by lipopolysaccharide-pulsed DC.
3700 17494064 Recognition of a defined region within p24 gag by CD8+ T cells during primary human immunodeficiency virus type 1 infection in individuals expressing protective HLA class I alleles.
3701 17494064 Human immunodeficiency virus type 1 (HIV-1)-specific immune responses during primary HIV-1 infection appear to play a critical role in determining the ultimate speed of disease progression, but little is known about the specificity of the initial HIV-1-specific CD8(+) T-cell responses in individuals expressing protective HLA class I alleles.
3702 17494064 Recognition of a defined region within p24 gag by CD8+ T cells during primary human immunodeficiency virus type 1 infection in individuals expressing protective HLA class I alleles.
3703 17494064 Human immunodeficiency virus type 1 (HIV-1)-specific immune responses during primary HIV-1 infection appear to play a critical role in determining the ultimate speed of disease progression, but little is known about the specificity of the initial HIV-1-specific CD8(+) T-cell responses in individuals expressing protective HLA class I alleles.
3704 17505014 To determine whether the leukemia-associated Wilms tumor antigen (WT1) contributes to a graft-versus-leukemia (GVL) effect after allogeneic stem-cell transplantation (SCT) for acute lymphoblastic leukemia (ALL), we studied CD8(+) T-cell responses to WT1 in 10 human lymphocyte antigen (HLA)-A*0201-positive ALL patients during the early phase of immune recovery after SCT (days 30-120).
3705 17505014 Using WT1/HLA-A*0201 tetramers and intracellular interferon-gamma (IFN-gamma) staining, WT1(+) CD8(+) T-cell responses after SCT were found only in patients with detectable WT1 expression before SCT (5 of 7 vs. 0 of 3; P < .05).
3706 17505014 To monitor the kinetics of WT1(+) CD8(+) T-cell responses and disease regression after SCT, absolute WT1(+) CD8(+) T-cell numbers and WT1 expression were studied for each time point.
3707 17505014 The emergence of WT1(+) CD8(+) T cells was associated with a decrease in WT1 expression, suggesting a WT1-driven GVL effect.
3708 17505014 Loss of WT1(+) CD8(+) T-cell responses was associated with reappearance of WT1 transcripts, consistent with a molecular relapse (P < .001).
3709 17505014 WT1(+) CD8(+) T cells had a predominantly effector-memory phenotype (CD45RO(+) CD27(-)CD57(+)) and produced IFN-gamma.
3710 17505014 Our results support the immunogenicity of WT1 after SCT for ALL and highlight the potential for WT1 vaccines to boost GVL after SCT for ALL.
3711 17505014 To determine whether the leukemia-associated Wilms tumor antigen (WT1) contributes to a graft-versus-leukemia (GVL) effect after allogeneic stem-cell transplantation (SCT) for acute lymphoblastic leukemia (ALL), we studied CD8(+) T-cell responses to WT1 in 10 human lymphocyte antigen (HLA)-A*0201-positive ALL patients during the early phase of immune recovery after SCT (days 30-120).
3712 17505014 Using WT1/HLA-A*0201 tetramers and intracellular interferon-gamma (IFN-gamma) staining, WT1(+) CD8(+) T-cell responses after SCT were found only in patients with detectable WT1 expression before SCT (5 of 7 vs. 0 of 3; P < .05).
3713 17505014 To monitor the kinetics of WT1(+) CD8(+) T-cell responses and disease regression after SCT, absolute WT1(+) CD8(+) T-cell numbers and WT1 expression were studied for each time point.
3714 17505014 The emergence of WT1(+) CD8(+) T cells was associated with a decrease in WT1 expression, suggesting a WT1-driven GVL effect.
3715 17505014 Loss of WT1(+) CD8(+) T-cell responses was associated with reappearance of WT1 transcripts, consistent with a molecular relapse (P < .001).
3716 17505014 WT1(+) CD8(+) T cells had a predominantly effector-memory phenotype (CD45RO(+) CD27(-)CD57(+)) and produced IFN-gamma.
3717 17505014 Our results support the immunogenicity of WT1 after SCT for ALL and highlight the potential for WT1 vaccines to boost GVL after SCT for ALL.
3718 17511777 Ex vivo tetramer staining of CD8(+) T lymphocytes was used to monitor T cells specific for human leucocyte antigen (HLA)-A*0201-restricted influenza A haemagglutinin antigens before and after vaccination.
3719 17511777 HLA-A*0201(+) PTSD patients (n = 10) showed a significant increase of influenza-specific CD8 T cells after vaccination.
3720 17511777 Although those PTSD patients had a lower number of influenza-specific CD8(+) T cells before vaccination compared to HLA-A*0201(+) healthy controls (n = 6), there was no difference in influenza A antibody titre between PTSD patients and control subjects before vaccination.
3721 17511777 Ex vivo tetramer staining of CD8(+) T lymphocytes was used to monitor T cells specific for human leucocyte antigen (HLA)-A*0201-restricted influenza A haemagglutinin antigens before and after vaccination.
3722 17511777 HLA-A*0201(+) PTSD patients (n = 10) showed a significant increase of influenza-specific CD8 T cells after vaccination.
3723 17511777 Although those PTSD patients had a lower number of influenza-specific CD8(+) T cells before vaccination compared to HLA-A*0201(+) healthy controls (n = 6), there was no difference in influenza A antibody titre between PTSD patients and control subjects before vaccination.
3724 17511777 Ex vivo tetramer staining of CD8(+) T lymphocytes was used to monitor T cells specific for human leucocyte antigen (HLA)-A*0201-restricted influenza A haemagglutinin antigens before and after vaccination.
3725 17511777 HLA-A*0201(+) PTSD patients (n = 10) showed a significant increase of influenza-specific CD8 T cells after vaccination.
3726 17511777 Although those PTSD patients had a lower number of influenza-specific CD8(+) T cells before vaccination compared to HLA-A*0201(+) healthy controls (n = 6), there was no difference in influenza A antibody titre between PTSD patients and control subjects before vaccination.
3727 17513797 Human histocompatibility leukocyte Ags-A*0201 (HLA-A*0201) transgenic mice were immunized with plasmids encoding the T1D-associated autoantigens: 65 kDa glutamic acid decarboxylase (GAD) or insulinoma-associated protein 2 (IA-2).
3728 17513797 All of the nine-candidate epitopes (five for GAD and four for IA-2) identified by our experimental approach were specifically recognized by CD8(+) T cells from newly diagnosed T1D patients (n = 19) but not from CD8(+) T cells of healthy controls (n = 20).
3729 17513797 Among these, GAD(114-123), GAD(536-545) and IA-2(805-813) were recognized by 53%, 25%, and 42% of T1D patients, respectively.
3730 17517052 In addition, the tumor tissues were subjected to immunohistochemical analysis to determine whether MIB-1, p53, and major histocompatibility complex (MHC) class-I complex expression could predict the response to the treatment.
3731 17517052 Low p53 and high MHC class-I expression by the tumor may help predict the efficacy of this therapy.
3732 17517052 In addition, the tumor tissues were subjected to immunohistochemical analysis to determine whether MIB-1, p53, and major histocompatibility complex (MHC) class-I complex expression could predict the response to the treatment.
3733 17517052 Low p53 and high MHC class-I expression by the tumor may help predict the efficacy of this therapy.
3734 17532057 Human peripheral blood CD14(+) monocytes were purified by using a magnetic separation column and cultured with GM-CSF and IL-4 to differentiate into immature DCs (iDCs).
3735 17532057 In the presence of Talpha1, iDC surface markers CD40, CD80, MHC class I and class II molecules were significantly upregulated as measured by flow cytemotry analysis.
3736 17532057 Thus, Talpha1 significantly enhances DC differentiation, activation, and functions from human peripheral blood CD14(+) monocytes possibly through a mechanism of the activation of p38 MAPK and NFkappaB pathways.
3737 17548610 Hsp90 inhibition significantly decreased cell surface expression of costimulatory (CD40, CD80, CD86), maturation (CD83), and MHC (HLA-A, B, C and HLA-DP, DQ, DR) markers in immature DC and mature DC and was associated with down-regulation of both RNA and intracellular protein expression.
3738 17548627 A comprehensive analysis of 18 viral proteins recognized by CD8(+) T cell responses demonstrated that approximately one-fortieth of all possible 9- to 10-mer peptides were high-affinity HLA-A*0201 binders.
3739 17549258 Using MHC tetramers, HA-specific CD4(+) T cells were detected among 25.0% (3 of 12) and 42.9% (6 of 14) of cord blood specimens possessing DRB1*0101 and DRB1*0401 HLA types, respectively, and were detected even when the DRB1 HLA type was inherited from the father.
3740 17549258 Matrix protein-specific CD8(+) T cells were detected among 10.0% (2 of 20) of HLA-A*0201(+) newborns.
3741 17549258 Using MHC tetramers, HA-specific CD4(+) T cells were detected among 25.0% (3 of 12) and 42.9% (6 of 14) of cord blood specimens possessing DRB1*0101 and DRB1*0401 HLA types, respectively, and were detected even when the DRB1 HLA type was inherited from the father.
3742 17549258 Matrix protein-specific CD8(+) T cells were detected among 10.0% (2 of 20) of HLA-A*0201(+) newborns.
3743 17562620 In a phase I clinical trial of biweekly vaccination with HLA-A*2402-restricted WT1 peptide for these malignancies, 2 patients with MDS developed severe leukocytopenia in association with a reduction in leukemic blast cells and levels of WT1 messenger RNA (mRNA) after only a single vaccination with 0.3 mg of WT1 peptide.
3744 17564703 Low TCR avidity and lack of tumor cell recognition in CD8(+) T cells primed with the CEA-analogue CAP1-6D peptide.
3745 17564703 In the present study, we show that CAP1-6D, a superagonist analogue of a carcinoembriyonic antigen (CEA)-derived HLA-A*0201-restricted epitope widely used in clinical setting, reproducibly promotes the generation of low-affinity CD8(+) T cells lacking the ability to recognized CEA-expressing colorectal carcinoma (CRC) cells.
3746 17564703 Short-term T cell cultures, obtained by priming peripheral blood mononuclear cells from HLA-A*0201(+) healthy donors or CRC patients with CAP1-6D, were indeed found to heterogeneously cross-react with saturating concentrations of the native peptide CAP1, but to fail constantly lysing or recognizing through IFN- gamma release CEA(+)CRC cells.
3747 17564703 Characterization of anti-CAP1-6D T cell avidity, gained through peptide titration, CD8-dependency assay, and staining with mutated tetramers (D227K/T228A), revealed that anti-CAP1-6D T cells exerted a differential interaction with the two CEA epitopes, i.e., displaying high affinity/CD8-independency toward the APL and low affinity/CD8-dependency toward the native CAP1 peptide.
3748 17564703 Low TCR avidity and lack of tumor cell recognition in CD8(+) T cells primed with the CEA-analogue CAP1-6D peptide.
3749 17564703 In the present study, we show that CAP1-6D, a superagonist analogue of a carcinoembriyonic antigen (CEA)-derived HLA-A*0201-restricted epitope widely used in clinical setting, reproducibly promotes the generation of low-affinity CD8(+) T cells lacking the ability to recognized CEA-expressing colorectal carcinoma (CRC) cells.
3750 17564703 Short-term T cell cultures, obtained by priming peripheral blood mononuclear cells from HLA-A*0201(+) healthy donors or CRC patients with CAP1-6D, were indeed found to heterogeneously cross-react with saturating concentrations of the native peptide CAP1, but to fail constantly lysing or recognizing through IFN- gamma release CEA(+)CRC cells.
3751 17564703 Characterization of anti-CAP1-6D T cell avidity, gained through peptide titration, CD8-dependency assay, and staining with mutated tetramers (D227K/T228A), revealed that anti-CAP1-6D T cells exerted a differential interaction with the two CEA epitopes, i.e., displaying high affinity/CD8-independency toward the APL and low affinity/CD8-dependency toward the native CAP1 peptide.
3752 17565417 Islet antigens are presented by human leukocyte antigen (HLA) class I and II molecules and are recognized by CD8(+) and CD4(+) autoreactive T cells in type 1 diabetic individuals.
3753 17579261 In this study, we treated three patients with renal cell carcinoma with an anchor modified, HLA-A*2402 binding WT1 peptide which was emulsified in Freund's incomplete adjuvant.
3754 17582562 Typhi oral vaccines include lymphoproliferation; production of type 1 cytokines (e.g., interferon- gamma and tumor necrosis factor- alpha ); and classical major histocompatibility complex (MHC) class Ia-restricted and novel, nonclassical MHC class Ib (human leukocyte antigen [HLA]-E)-restricted CD8(+) cytotoxic T cell responses.
3755 17610503 Addition of TAT protein transduction domain and GrpE to human p53 provides soluble fusion proteins that can be transduced into dendritic cells and elicit p53-specific T-cell responses in HLA-A*0201 transgenic mice.
3756 17610503 The protein p53 has been shown to be an efficient tumour antigen in both murine and human cancer vaccine studies and cancer vaccines targeting p53 based on major histocompatibility complex (MHC) class I binding p53-derived peptides that induce cytotoxic T lymphocytes (CTLs) without p53-specific CD4(+) T-cell help have been tested by several research groups including ours.
3757 17610503 To obtain such CD4(+) T-cell help and cover a broader repertoire of MHC haplotypes we have previously attempted to produce recombinant human p53 for vaccination purposes.
3758 17610503 Here, we show that fusion of an 11-amino-acid region of the human immunodeficiency virus TAT protein transduction domain (PTD) to human p53 increases the solubility of the otherwise insoluble p53 protein and this rTAT-p53 protein can be transduced into human monocyte-derived dendritic cells (DCs).
3759 17610503 The induction of a p53-specific HLA-A*0201 immune response was tested in HLA-A*0201/K(b) transgenic mice after immunization with rTAT-p53-transduced bone-marrow-derived DCs.
3760 17610503 In these mice, p53-specific CD4(+) and CD8(+) T-cell proliferation was observed and immunization resulted in the induction of HLA-A*0201-restricted CTLs specific for two human p53-derived HLA-A*0201-binding peptides, p53(65-73) and p53(149-157).
3761 17610503 Addition of TAT protein transduction domain and GrpE to human p53 provides soluble fusion proteins that can be transduced into dendritic cells and elicit p53-specific T-cell responses in HLA-A*0201 transgenic mice.
3762 17610503 The protein p53 has been shown to be an efficient tumour antigen in both murine and human cancer vaccine studies and cancer vaccines targeting p53 based on major histocompatibility complex (MHC) class I binding p53-derived peptides that induce cytotoxic T lymphocytes (CTLs) without p53-specific CD4(+) T-cell help have been tested by several research groups including ours.
3763 17610503 To obtain such CD4(+) T-cell help and cover a broader repertoire of MHC haplotypes we have previously attempted to produce recombinant human p53 for vaccination purposes.
3764 17610503 Here, we show that fusion of an 11-amino-acid region of the human immunodeficiency virus TAT protein transduction domain (PTD) to human p53 increases the solubility of the otherwise insoluble p53 protein and this rTAT-p53 protein can be transduced into human monocyte-derived dendritic cells (DCs).
3765 17610503 The induction of a p53-specific HLA-A*0201 immune response was tested in HLA-A*0201/K(b) transgenic mice after immunization with rTAT-p53-transduced bone-marrow-derived DCs.
3766 17610503 In these mice, p53-specific CD4(+) and CD8(+) T-cell proliferation was observed and immunization resulted in the induction of HLA-A*0201-restricted CTLs specific for two human p53-derived HLA-A*0201-binding peptides, p53(65-73) and p53(149-157).
3767 17610503 Addition of TAT protein transduction domain and GrpE to human p53 provides soluble fusion proteins that can be transduced into dendritic cells and elicit p53-specific T-cell responses in HLA-A*0201 transgenic mice.
3768 17610503 The protein p53 has been shown to be an efficient tumour antigen in both murine and human cancer vaccine studies and cancer vaccines targeting p53 based on major histocompatibility complex (MHC) class I binding p53-derived peptides that induce cytotoxic T lymphocytes (CTLs) without p53-specific CD4(+) T-cell help have been tested by several research groups including ours.
3769 17610503 To obtain such CD4(+) T-cell help and cover a broader repertoire of MHC haplotypes we have previously attempted to produce recombinant human p53 for vaccination purposes.
3770 17610503 Here, we show that fusion of an 11-amino-acid region of the human immunodeficiency virus TAT protein transduction domain (PTD) to human p53 increases the solubility of the otherwise insoluble p53 protein and this rTAT-p53 protein can be transduced into human monocyte-derived dendritic cells (DCs).
3771 17610503 The induction of a p53-specific HLA-A*0201 immune response was tested in HLA-A*0201/K(b) transgenic mice after immunization with rTAT-p53-transduced bone-marrow-derived DCs.
3772 17610503 In these mice, p53-specific CD4(+) and CD8(+) T-cell proliferation was observed and immunization resulted in the induction of HLA-A*0201-restricted CTLs specific for two human p53-derived HLA-A*0201-binding peptides, p53(65-73) and p53(149-157).
3773 17610503 Addition of TAT protein transduction domain and GrpE to human p53 provides soluble fusion proteins that can be transduced into dendritic cells and elicit p53-specific T-cell responses in HLA-A*0201 transgenic mice.
3774 17610503 The protein p53 has been shown to be an efficient tumour antigen in both murine and human cancer vaccine studies and cancer vaccines targeting p53 based on major histocompatibility complex (MHC) class I binding p53-derived peptides that induce cytotoxic T lymphocytes (CTLs) without p53-specific CD4(+) T-cell help have been tested by several research groups including ours.
3775 17610503 To obtain such CD4(+) T-cell help and cover a broader repertoire of MHC haplotypes we have previously attempted to produce recombinant human p53 for vaccination purposes.
3776 17610503 Here, we show that fusion of an 11-amino-acid region of the human immunodeficiency virus TAT protein transduction domain (PTD) to human p53 increases the solubility of the otherwise insoluble p53 protein and this rTAT-p53 protein can be transduced into human monocyte-derived dendritic cells (DCs).
3777 17610503 The induction of a p53-specific HLA-A*0201 immune response was tested in HLA-A*0201/K(b) transgenic mice after immunization with rTAT-p53-transduced bone-marrow-derived DCs.
3778 17610503 In these mice, p53-specific CD4(+) and CD8(+) T-cell proliferation was observed and immunization resulted in the induction of HLA-A*0201-restricted CTLs specific for two human p53-derived HLA-A*0201-binding peptides, p53(65-73) and p53(149-157).
3779 17610503 Addition of TAT protein transduction domain and GrpE to human p53 provides soluble fusion proteins that can be transduced into dendritic cells and elicit p53-specific T-cell responses in HLA-A*0201 transgenic mice.
3780 17610503 The protein p53 has been shown to be an efficient tumour antigen in both murine and human cancer vaccine studies and cancer vaccines targeting p53 based on major histocompatibility complex (MHC) class I binding p53-derived peptides that induce cytotoxic T lymphocytes (CTLs) without p53-specific CD4(+) T-cell help have been tested by several research groups including ours.
3781 17610503 To obtain such CD4(+) T-cell help and cover a broader repertoire of MHC haplotypes we have previously attempted to produce recombinant human p53 for vaccination purposes.
3782 17610503 Here, we show that fusion of an 11-amino-acid region of the human immunodeficiency virus TAT protein transduction domain (PTD) to human p53 increases the solubility of the otherwise insoluble p53 protein and this rTAT-p53 protein can be transduced into human monocyte-derived dendritic cells (DCs).
3783 17610503 The induction of a p53-specific HLA-A*0201 immune response was tested in HLA-A*0201/K(b) transgenic mice after immunization with rTAT-p53-transduced bone-marrow-derived DCs.
3784 17610503 In these mice, p53-specific CD4(+) and CD8(+) T-cell proliferation was observed and immunization resulted in the induction of HLA-A*0201-restricted CTLs specific for two human p53-derived HLA-A*0201-binding peptides, p53(65-73) and p53(149-157).
3785 17611570 Computer algorithms that in silico predict HLA class I and class II binding, proteasome cleavage patterns and transporter associated with antigen processing translocation are now available to expedite epitope identification.
3786 17619750 Human cytotoxic T lymphocytes (CTLs), which could specifically lyse WT1-expressing tumor cells with HLA class I restriction, were generated in vitro.
3787 17619750 CD8+ WT1-specific CTLs were also detected in peripheral blood or tumor-draining lymph nodes of cancer patients.
3788 17631051 Toward the development of multi-epitope p53 cancer vaccines: an in vitro assessment of CD8(+) T cell responses to HLA class I-restricted wild-type sequence p53 peptides.
3789 17631051 Peripheral blood mononuclear cells (PBMC) obtained from HLA-A*0201(+) and/or HLA-A*2402(+) normal donors and subjects with squamous cell carcinoma of the head and neck (SCCHN) were analyzed for p53 peptide-specific reactivity in ELISPOT IFN-gamma assays.
3790 17631051 CD8(+) T cells in 7/10 normal donors (HD) and 11/23 subjects with SCCHN responded to at least one of the wt p53 peptides.
3791 17631051 CD8(+) T cell precursors responsive to wt p53 epitopes were detected in the circulation of most subjects with early disease, and an elevated blood Tc(1)/Tc(2) ratio distinguished wt p53 peptide responders from non-responders.
3792 17631051 Toward the development of multi-epitope p53 cancer vaccines: an in vitro assessment of CD8(+) T cell responses to HLA class I-restricted wild-type sequence p53 peptides.
3793 17631051 Peripheral blood mononuclear cells (PBMC) obtained from HLA-A*0201(+) and/or HLA-A*2402(+) normal donors and subjects with squamous cell carcinoma of the head and neck (SCCHN) were analyzed for p53 peptide-specific reactivity in ELISPOT IFN-gamma assays.
3794 17631051 CD8(+) T cells in 7/10 normal donors (HD) and 11/23 subjects with SCCHN responded to at least one of the wt p53 peptides.
3795 17631051 CD8(+) T cell precursors responsive to wt p53 epitopes were detected in the circulation of most subjects with early disease, and an elevated blood Tc(1)/Tc(2) ratio distinguished wt p53 peptide responders from non-responders.
3796 17652518 Vaccination with an NY-ESO-1 peptide of HLA class I/II specificities induces integrated humoral and T cell responses in ovarian cancer.
3797 17652518 The NY-ESO-1 peptide epitope, ESO(157-170), is recognized by HLA-DP4-restricted CD4+ T cells and HLA-A2- and A24-restricted CD8+ T cells.
3798 17652518 NY-ESO-1-specific Ab responses and/or specific HLA-A2-restricted CD8+ and HLA-DP4-restricted CD4+ T cell responses were induced by a course of at least five vaccinations at three weekly intervals in a high proportion of patients.
3799 17652518 Vaccine-induced CD8+ and CD4+ T cell clones were shown to recognize NY-ESO-1-expressing tumor targets.
3800 17652518 Long-lived and functional vaccine-elicited CD8+ and CD4+ T cells were detectable in some patients up to 12 months after immunization.
3801 17652518 These results confirm the paradigm that the provision of cognate CD4+ T cell help is important for cancer vaccine design and provides the rationale for a phase II study design using ESO(157-170) epitope or the full-length NY-ESO-1 protein for immunotherapy in patients with EOC.
3802 17668898 Immunisation of transgenic mice with a preparation of these six regions as chemically synthesised peptides (FLU-v) induced a specific HLA-A*0201-mediated CD8(+) T cell response.
3803 17686874 Using ex vivo antigen-specific T-cell analysis, we found that symptomatic cytomegalovirus recrudescence in transplant recipients was coincident with reduced expression of gamma interferon (IFN-gamma) by virus-specific CD8(+) T cells and an up-regulation of CD38 expression on these T cells, although there was no significant change in the absolute number of virus-specific cells (as assessed by major histocompatibility complex-peptide multimers).
3804 17686874 In contrast, HLA class I-matched transplant patients with asymptomatic viral recrudescence showed increased expansion of antigen-specific T cells and highly stable IFN-gamma expression by epitope-specific T cells.
3805 17698917 As expected, TLR agonists, such as LPS (TLR4) and fibroblast-stimulating lipopeptide-1 (FSL-1; TLR2), induced macrophage activation and increased macrophage killing of phase II C. burnetii in vitro.
3806 17698917 Securinine, a gamma-aminobutyric acid type A receptor antagonist, was found to induce TLR-independent macrophage activation in vitro, leading to IL-8 secretion, L-selectin down-regulation, and CD11b and MHC Class II antigen up-regulation.
3807 17725421 While peptides that were most frequently recognized by the CTL response in Nef and p24 tended to be conserved, this was not the case for p17 where epitope recognition coincided with highly variable regions.
3808 17725421 Only 52% of the Nef peptides and 64% of the Gag peptides that elicited a CTL response contained sequence motifs thought to be required for binding by the HLA-A or -B alleles found in the corresponding patient.
3809 17726460 Eighteen human leukocyte antigen (HLA)-A*0201(+) melanoma patients were randomized as follows: one group received three mouse TYR DNA injections followed by three human TYR DNA injections; the other group received the same vaccines in opposite sequence.
3810 17726460 Seven patients developed CD8(+) T-cell responses, defined by a >3 SD increase in baseline reactivity to TYR peptide in tetramer or intracellular cytokine staining (ICS) assays.
3811 17726460 Mouse and human TYR DNA vaccines were found safe and induced CD8(+) T-cell responses in 7 of 18 patients.
3812 17767547 We therefore extensively review the current technologies of antigen presentation prediction, including the next generation predictors, which combine proteasomal processing, transporter associated with antigen processing and major histocompatibility complex (MHC)-binding prediction.
3813 17784873 For the development of cancer vaccine therapies, we have searched for possible epitope peptides that can elicit cytotoxic T lymphocytes (CTL) to the TTK protein kinase (TTK), lymphocyte antigen 6 complex locus K (LY6K) and insulin-like growth factor (IGF)-II mRNA binding protein 3 (IMP-3), which were previously identified to be transactivated in the majority of lung and esophageal cancers.
3814 17784873 We screened 31, 17 and 17 candidate human leukocyte antigen (HLA)-A*2402-binding peptides to parts of TTK, LY6K and IMP-3, respectively.
3815 17784873 Subsequent analysis of the CTL clones also revealed their cytotoxic activities against lung and esophageal tumor cells that endogenously express TTK, LY6K or IMP-3.
3816 17784873 Our results strongly imply that TTK, LY6K and IMP-3 are novel tumor-associated antigens recognized by CTL, and TTK-567 (SYRNEIAYL), LY6K-177 (RYCNLEGPPI) and IMP-3-508 (KTVNELQNL) are HLA-A24-restricted epitope peptides that can induce potent and specific immune responses against lung and esophageal cancer cells expressing TTK, LY6K and IMP-3.
3817 17786175 From a clinical perspective, convincing data indicate that epigenetic modulatory agents, including DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors, robustly promote the expression of CG antigens, as well as class I major histocompatibility complex (MHC I) and other immune costimulatory molecules, in tumors.
3818 17786443 Here, we tested our hypothesis that suppression of TAMs can be achieved in syngeneic BALB/c mice with oral minigene vaccines against murine MHC class I antigen epitopes of Legumain, an asparaginyl endopeptidase and a member of the C13 family of cystine proteases which is overexpressed on TAMs in the tumor stroma.
3819 17786443 We demonstrated that the Legumain minigene vaccine provided effective protection against tumor cell challenge by inducing a specific CD8+ T-cell response against Legumain+ TAMs in our breast tumor model.
3820 17850587 Antigen (Ag)-presenting and co-stimulatory capacity of neonatal B-cells was evaluated by staining for major histocompatibility complex (MHC)II, CD80, CD86 and CD40.
3821 17850587 Spleen cells from mice receiving LT-K63 showed enhanced proliferation and interferon (IFN)-gamma, interleukin (IL)-4, IL-5 and IL-10 secretion upon TT stimulation, whereas cells from mice receiving CpG2006 could only enhance IL-10 secretion.
3822 17874294 Characterization of the role of CD8+T cells in breast cancer immunity following mammaglobin-A DNA vaccination using HLA-class-I tetramers.
3823 17875682 A large proportion of human cancers show deficiencies in the MHC class I antigen-processing machinery.
3824 17875804 Leukemia-associated antigen-specific T-cell responses following combined PR1 and WT1 peptide vaccination in patients with myeloid malignancies.
3825 17875804 We describe the safety and immunogenicity of a combined vaccine of 2 leukemia-associated antigenic peptides, PR1 and WT1.
3826 17875804 Eight patients with myeloid malignancies received one subcutaneous dose each of PR1 and WT1 vaccines in Montanide adjuvant, with granulocyte-macrophage colony-stimulating factor.
3827 17875804 Using peptide/HLA-A 0201 tetramers and intracellular interferon-gamma staining, CD8(+) T cells against PR1 or WT1 were detected in 8 of 8 patients after a single vaccination.
3828 17875804 To monitor the kinetics of vaccine-induced CD8(+) T-cell responses and disease regression after vaccination, absolute PR1 and WT1(+)CD8(+) T-cell numbers and WT1 expression were studied weekly after vaccination.
3829 17875804 After vaccination, the emergence of PR1 or WT1(+)CD8(+) T cells was associated with a decrease in WT1 mRNA expression as a marker of minimal residual disease, suggesting a vaccine-driven antileukemia effect.
3830 17875804 This is the first demonstration that a combined PR1 and WT1 vaccine is immunogenic.
3831 17892322 Immunodominant tuberculosis CD8 antigens preferentially restricted by HLA-B.
3832 17892322 First, using IFN-gamma ELISPOT and synthetic peptide arrays as a source of antigen, we measured ex vivo frequencies of CD8(+) T cells recognizing known immunodominant CD4(+) T cell antigens in persons with latent tuberculosis infection.
3833 17892322 In all cases, peptide representing the minimal epitope bound to the major histocompatibility complex (MHC)-restricting allele with high affinity, and in all but one case the restricting allele was an HLA-B allele.
3834 17892322 We conclude that Mtb-specific CD8(+) T cells are found in high frequency in infected individuals and are restricted predominantly by HLA-B alleles, and that synthetic peptide arrays can be used to define epitope specificities without prior bias as to MHC binding affinity.
3835 17892322 Immunodominant tuberculosis CD8 antigens preferentially restricted by HLA-B.
3836 17892322 First, using IFN-gamma ELISPOT and synthetic peptide arrays as a source of antigen, we measured ex vivo frequencies of CD8(+) T cells recognizing known immunodominant CD4(+) T cell antigens in persons with latent tuberculosis infection.
3837 17892322 In all cases, peptide representing the minimal epitope bound to the major histocompatibility complex (MHC)-restricting allele with high affinity, and in all but one case the restricting allele was an HLA-B allele.
3838 17892322 We conclude that Mtb-specific CD8(+) T cells are found in high frequency in infected individuals and are restricted predominantly by HLA-B alleles, and that synthetic peptide arrays can be used to define epitope specificities without prior bias as to MHC binding affinity.
3839 17947674 The IL-10(-/-)DCs were highly immunogenic, expressed enhanced levels of surface MHC class II molecules, and secreted increased amounts of Th1-related cytokines.
3840 17981331 A classic feature of antigen presentation for CD8+ T cell recognition is that MHC class I molecules generally present peptides of 8-10 amino acids in length.
3841 17982631 Antibody blocking and cold inhibition experiments confirmed that the cytotoxicity was partially ascribed to peptide-specific and HLA class I-restricted CD8+ T cells.
3842 17982663 We used imaging means to demonstrate the conservation of presentation molecules (MHC II, CD1a), co-stimulatory molecules (CD40, CD80, CD86), as well as tumour antigens (Her2/neu, cytokeratins) in optimised conditions.
3843 17989341 Human leukocyte antigens (HLA-A, HLA-B, and HLA-DRB1), four lymphotoxin alpha single-nucleotide polymorphisms, and complement C4A and C4B allotypes were typed, and their haplotypes were inferred.
3844 17989341 Smokers with HLA-B*35 or HLA-A*03-B*35 had markers of C. pneumoniae infection that appeared more often than in smokers without these genes (P = 0.003 and P = 0.001, respectively).
3845 17989341 Human leukocyte antigens (HLA-A, HLA-B, and HLA-DRB1), four lymphotoxin alpha single-nucleotide polymorphisms, and complement C4A and C4B allotypes were typed, and their haplotypes were inferred.
3846 17989341 Smokers with HLA-B*35 or HLA-A*03-B*35 had markers of C. pneumoniae infection that appeared more often than in smokers without these genes (P = 0.003 and P = 0.001, respectively).
3847 17991045 We show here that exposure of human DC to live meningococci does not result in a typical maturation response, as determined by the failure to upregulate CD40, CD86, HLA-DR and HLA-Class I.
3848 17991045 Despite this, live meningococci were potent inducers of IL-12 and IL-10, although the ratios of these cytokines differed from those to killed organisms.
3849 17992938 The incidence of IBV respiratory signs was significantly higher in B2/21 than in B2/B15 MHC genotype birds.
3850 17997122 The modification induced structural changes in most modified HABPs, changing them from random-coil or distorted type III beta-turn structures to classical type III or III' beta-turn, thereby allowing a better fit into the MHC-II-peptide-TCR complex since they bound with high affinity to purified HLA-DRbeta1* molecules.
3851 17997122 These are the first (TRAP) conserved HABPs corresponding to functionally active amino acid sequences in sporozoite invasion and mobility which, when modified, were able to induce very high anti-sporozoite antibody responses, leading to suggesting them as components in the first line of defence of a fully-effective, subunit-based, multi-epitope, multi-stage, synthetic anti-malarial vaccine.
3852 18020497 Approaches evaluated include the use of T cell receptor peptide vaccines, autologous T cells, major histocompatibility complex (MHC) peptides, allogeneic mononuclear cells and oral collagen.
3853 18020497 These include placenta-eluted gamma globulins (which contain antibodies to HLA-DR antigens), DR4/DR1 peptide vaccines and allogeneic mononuclear cell vaccination.
3854 18043580 In this study, we attempted to identify cytotoxic T lymphocyte (CTL)-directed Lck-derived peptides applicable to HLA-A11(+), -A31(+), or -A33(+) cancer patients, because these HLA-A alleles share binding motifs, designated HLA-A3 supertype alleles, and because the Lck is preferentially expressed in metastatic cancer.
3855 18043580 Their cytotoxicity towards cancer cells was mainly ascribed to HLA class I-restricted and peptide-specific CD8(+) T cells.
3856 18043580 In this study, we attempted to identify cytotoxic T lymphocyte (CTL)-directed Lck-derived peptides applicable to HLA-A11(+), -A31(+), or -A33(+) cancer patients, because these HLA-A alleles share binding motifs, designated HLA-A3 supertype alleles, and because the Lck is preferentially expressed in metastatic cancer.
3857 18043580 Their cytotoxicity towards cancer cells was mainly ascribed to HLA class I-restricted and peptide-specific CD8(+) T cells.
3858 18070892 Six antigens targeted by CD8 T cells from T. parva-immune cattle of different major histocompatibility complex (MHC) genotypes have been identified, raising the prospect of developing a subunit vaccine.
3859 18070892 To facilitate further dissection of the specificity of protective CD8 T-cell responses and to assist in the assessment of responses to vaccination, we set out to identify the epitopes recognized in these T. parva antigens and their MHC restriction elements.
3860 18070892 Six antigens targeted by CD8 T cells from T. parva-immune cattle of different major histocompatibility complex (MHC) genotypes have been identified, raising the prospect of developing a subunit vaccine.
3861 18070892 To facilitate further dissection of the specificity of protective CD8 T-cell responses and to assist in the assessment of responses to vaccination, we set out to identify the epitopes recognized in these T. parva antigens and their MHC restriction elements.
3862 18097044 HLA-A*0201-restricted CD8+ cytotoxic T lymphocyte epitopes identified from herpes simplex virus glycoprotein D.
3863 18097044 However, knowledge of gD-specific human T cell responses is limited to CD4+ T cell epitopes, with no CD8+ T cell epitopes identified to date.
3864 18097044 In this study, we screened the HSV-1 gD amino acid sequence for HLA-A*0201-restricted epitopes using several predictive computational algorithms and identified 10 high probability CD8+ T cell epitopes.
3865 18097044 Consistent with this, in 33 sequentially studied HLA-A*0201-positive, HSV-1-seropositive, and/or HSV-2-seropositive healthy individuals, the most frequent and robust CD8+ T cell responses, assessed by IFN-gamma ELISPOT, CD107a/b cytotoxic degranulation, and tetramer assays, were directed mainly against gD53-61, gD70-78, and gD278-286 epitopes.
3866 18097044 Lastly, CD8+ T cell responses specific to gD53-61, gD70-78, and gD278-286 epitopes were induced in HLA-A*0201 transgenic mice following ocular or genital infection with either HSV-1 or HSV-2.
3867 18097044 HLA-A*0201-restricted CD8+ cytotoxic T lymphocyte epitopes identified from herpes simplex virus glycoprotein D.
3868 18097044 However, knowledge of gD-specific human T cell responses is limited to CD4+ T cell epitopes, with no CD8+ T cell epitopes identified to date.
3869 18097044 In this study, we screened the HSV-1 gD amino acid sequence for HLA-A*0201-restricted epitopes using several predictive computational algorithms and identified 10 high probability CD8+ T cell epitopes.
3870 18097044 Consistent with this, in 33 sequentially studied HLA-A*0201-positive, HSV-1-seropositive, and/or HSV-2-seropositive healthy individuals, the most frequent and robust CD8+ T cell responses, assessed by IFN-gamma ELISPOT, CD107a/b cytotoxic degranulation, and tetramer assays, were directed mainly against gD53-61, gD70-78, and gD278-286 epitopes.
3871 18097044 Lastly, CD8+ T cell responses specific to gD53-61, gD70-78, and gD278-286 epitopes were induced in HLA-A*0201 transgenic mice following ocular or genital infection with either HSV-1 or HSV-2.
3872 18097044 HLA-A*0201-restricted CD8+ cytotoxic T lymphocyte epitopes identified from herpes simplex virus glycoprotein D.
3873 18097044 However, knowledge of gD-specific human T cell responses is limited to CD4+ T cell epitopes, with no CD8+ T cell epitopes identified to date.
3874 18097044 In this study, we screened the HSV-1 gD amino acid sequence for HLA-A*0201-restricted epitopes using several predictive computational algorithms and identified 10 high probability CD8+ T cell epitopes.
3875 18097044 Consistent with this, in 33 sequentially studied HLA-A*0201-positive, HSV-1-seropositive, and/or HSV-2-seropositive healthy individuals, the most frequent and robust CD8+ T cell responses, assessed by IFN-gamma ELISPOT, CD107a/b cytotoxic degranulation, and tetramer assays, were directed mainly against gD53-61, gD70-78, and gD278-286 epitopes.
3876 18097044 Lastly, CD8+ T cell responses specific to gD53-61, gD70-78, and gD278-286 epitopes were induced in HLA-A*0201 transgenic mice following ocular or genital infection with either HSV-1 or HSV-2.
3877 18097044 HLA-A*0201-restricted CD8+ cytotoxic T lymphocyte epitopes identified from herpes simplex virus glycoprotein D.
3878 18097044 However, knowledge of gD-specific human T cell responses is limited to CD4+ T cell epitopes, with no CD8+ T cell epitopes identified to date.
3879 18097044 In this study, we screened the HSV-1 gD amino acid sequence for HLA-A*0201-restricted epitopes using several predictive computational algorithms and identified 10 high probability CD8+ T cell epitopes.
3880 18097044 Consistent with this, in 33 sequentially studied HLA-A*0201-positive, HSV-1-seropositive, and/or HSV-2-seropositive healthy individuals, the most frequent and robust CD8+ T cell responses, assessed by IFN-gamma ELISPOT, CD107a/b cytotoxic degranulation, and tetramer assays, were directed mainly against gD53-61, gD70-78, and gD278-286 epitopes.
3881 18097044 Lastly, CD8+ T cell responses specific to gD53-61, gD70-78, and gD278-286 epitopes were induced in HLA-A*0201 transgenic mice following ocular or genital infection with either HSV-1 or HSV-2.
3882 18156189 MART-1-modified peptide (A27L peptide) and apoptotic HLA-A*0201-positive, MART-1-positive JCOCB tumor cell lines were used as tumor antigen sources.
3883 18192109 The patient received weekly intradermal injections of an HLA-A*2402-restricted 9-mer WT1 peptide emulsified with Montanide ISA 51 adjuvant for 12 weeks and achieved a minimal response according to European Group for Blood and Marrow Transplantation criteria without experiencing systemic adverse effects.
3884 18192109 As for immunologic parameters, the frequency of WT1 tetramer-positive cells among CD8+ T-cells, which was higher than in healthy donors, temporarily decreased at weeks 4 and 8 but increased at week 12, whereas the frequency of WT1 peptide-responding CD107a/b+ cells among WT1 tetramer-positive T-cells increased from 27.0% to 38.6% after the vaccination.
3885 18198367 Exogenous introduction of particle-associated proteins of human cytomegalovirus (HCMV) into the major histocompatibility complex (MHC) class I presentation pathway by subviral dense bodies (DB) is an effective way to sensitize cells against CD8 T-cell (CTL) recognition and killing.
3886 18206244 Peptide-binding motif prediction by using phage display library for SasaUBA*0301, a resistance haplotype of MHC class I molecule from Atlantic Salmon (Salmo salar).
3887 18206244 Phage display technology using both 7 mer and 12 mer libraries enabled us to identify peptide ligands with unique specificity that interacts with the recombinant Salmon MHC class I molecule.
3888 18206244 Peptide-binding motif prediction by using phage display library for SasaUBA*0301, a resistance haplotype of MHC class I molecule from Atlantic Salmon (Salmo salar).
3889 18206244 Phage display technology using both 7 mer and 12 mer libraries enabled us to identify peptide ligands with unique specificity that interacts with the recombinant Salmon MHC class I molecule.
3890 18212086 We identified a novel HLA-A*0201-restricted CD8+ T-cell epitope on a dominant secreted antigen of M. tuberculosis, MPT51, in HLA-A*0201 transgenic HHD mice.
3891 18212086 Three-color flow cytometric analysis of intracellular IFN-gamma and cell surface CD4 and CD8 staining revealed that the MPT51 p51-70 peptide contains an immunodominant CD8+ T-cell epitope.
3892 18212086 In addition, MPT51 p53-62-specific memory CD8+ T cells were found in tuberculin skin test-positive HLA-A*0201+ healthy individuals.
3893 18212086 Use of this HLA-A*0201-restricted CD8+ T-cell epitope for analysis of the role of MPT51-specific T cells in M. tuberculosis infection and for design of vaccines against tuberculosis is feasible.
3894 18212086 We identified a novel HLA-A*0201-restricted CD8+ T-cell epitope on a dominant secreted antigen of M. tuberculosis, MPT51, in HLA-A*0201 transgenic HHD mice.
3895 18212086 Three-color flow cytometric analysis of intracellular IFN-gamma and cell surface CD4 and CD8 staining revealed that the MPT51 p51-70 peptide contains an immunodominant CD8+ T-cell epitope.
3896 18212086 In addition, MPT51 p53-62-specific memory CD8+ T cells were found in tuberculin skin test-positive HLA-A*0201+ healthy individuals.
3897 18212086 Use of this HLA-A*0201-restricted CD8+ T-cell epitope for analysis of the role of MPT51-specific T cells in M. tuberculosis infection and for design of vaccines against tuberculosis is feasible.
3898 18212086 We identified a novel HLA-A*0201-restricted CD8+ T-cell epitope on a dominant secreted antigen of M. tuberculosis, MPT51, in HLA-A*0201 transgenic HHD mice.
3899 18212086 Three-color flow cytometric analysis of intracellular IFN-gamma and cell surface CD4 and CD8 staining revealed that the MPT51 p51-70 peptide contains an immunodominant CD8+ T-cell epitope.
3900 18212086 In addition, MPT51 p53-62-specific memory CD8+ T cells were found in tuberculin skin test-positive HLA-A*0201+ healthy individuals.
3901 18212086 Use of this HLA-A*0201-restricted CD8+ T-cell epitope for analysis of the role of MPT51-specific T cells in M. tuberculosis infection and for design of vaccines against tuberculosis is feasible.
3902 18220508 We also describe a new experimental vaccine model for the generation of CD8+ cytotoxic T cells (CTL) that involves designer TACA-containing glycopeptides with high affinity for class I molecules of the major histocompatibility complex (MHC).
3903 18245488 Our results show the induction of an immune response against a newly defined PSCA epitope that is mediated primarily by CD8 T cells.
3904 18245488 The prostates of PSCA-vaccinated mice were infiltrated by CD4-positive, CD8-positive, CD11b-positive, and CD11c-positive cells.
3905 18245488 Vaccination induced MHC class I expression and cytokine production [IFN-gamma, tumor necrosis factor-alpha, interleukin 2 (IL-2), IL-4, and IL-5] within prostate tumors.
3906 18248530 Overall, our results demonstrate the presence of HLA class I-restricted CD8+ CTL against proteins from PE and PPE proteins of M. tuberculosis and identify epitopes that are strongly recognized by HLA-A*0201-restricted CD8+ T cells in humans.
3907 18250455 These MHC class II-bound peptides were recognized by Chlamydia-specific CD4 T cells harvested from immune mice and adoptive transfer of dendritic cells pulsed ex vivo with the peptides partially protected mice against intranasal and genital tract Chlamydia infection.
3908 18253733 Recognition of naturally processed and ovarian cancer reactive CD8+ T cell epitopes within a promiscuous HLA class II T-helper region of NY-ESO-1.
3909 18253733 The identification of NY-ESO-1 peptide epitopes with dual HLA-class I and class II specificities might be useful in vaccination strategies for generating cognate CD4+ T cell help to augment CD8+ T cell responses.
3910 18253733 Here, we describe two novel NY-ESO-1-derived MHC class I epitopes from EOC patients with spontaneous humoral immune response to NY-ESO-1.
3911 18253733 CD8+ T cells derived from NY-ESO-1 seropositive EOC patients were presensitized with a recombinant adenovirus encoding NY-ESO-1or pooled overlapping peptides.
3912 18253733 Recognition of naturally processed and ovarian cancer reactive CD8+ T cell epitopes within a promiscuous HLA class II T-helper region of NY-ESO-1.
3913 18253733 The identification of NY-ESO-1 peptide epitopes with dual HLA-class I and class II specificities might be useful in vaccination strategies for generating cognate CD4+ T cell help to augment CD8+ T cell responses.
3914 18253733 Here, we describe two novel NY-ESO-1-derived MHC class I epitopes from EOC patients with spontaneous humoral immune response to NY-ESO-1.
3915 18253733 CD8+ T cells derived from NY-ESO-1 seropositive EOC patients were presensitized with a recombinant adenovirus encoding NY-ESO-1or pooled overlapping peptides.
3916 18266328 The three-dimensional (3D) structure of >100 of these native modified HABPs (determined by (1)H NMR) revealed that the following structural changes had all to be achieved to allow a better fit into the major histocompatibility complex class II (MHC II)-peptide-TCR complex to properly activate the immune system: alpha-helix shortening, modifying their beta-turn, adopting segmental alpha-helix configuration, changing residue orientation, and increasing the distance of those residues fitting into the MHC II molecules from antigen-presenting cells.
3917 18272757 An MHC-restricted CD8+ T-cell response is induced in cattle by foot-and-mouth disease virus (FMDV) infection and also following vaccination with inactivated FMDV.
3918 18272757 This study aimed to investigate major histocompatibility complex (MHC) class I-restricted CD8(+) T-cell responses to FMDV in vaccinated and in infected cattle.
3919 18272757 An in vitro assay was used to detect antigen-specific gamma interferon release by CD8(+) T cells in FMDV-infected cattle of known MHC class I genotypes.
3920 18272757 A significant MHC class I-restricted CD8(+) T-cell response was detected to both FMDV strain O1 BFS and a recombinant fowlpox virus expressing the structural proteins of FMDV.
3921 18272757 Antigen-specific MHC class I-restricted CD8(+) T-cell responses were also detected in cattle vaccinated with inactivated FMDV.
3922 18272757 An MHC-restricted CD8+ T-cell response is induced in cattle by foot-and-mouth disease virus (FMDV) infection and also following vaccination with inactivated FMDV.
3923 18272757 This study aimed to investigate major histocompatibility complex (MHC) class I-restricted CD8(+) T-cell responses to FMDV in vaccinated and in infected cattle.
3924 18272757 An in vitro assay was used to detect antigen-specific gamma interferon release by CD8(+) T cells in FMDV-infected cattle of known MHC class I genotypes.
3925 18272757 A significant MHC class I-restricted CD8(+) T-cell response was detected to both FMDV strain O1 BFS and a recombinant fowlpox virus expressing the structural proteins of FMDV.
3926 18272757 Antigen-specific MHC class I-restricted CD8(+) T-cell responses were also detected in cattle vaccinated with inactivated FMDV.
3927 18272757 An MHC-restricted CD8+ T-cell response is induced in cattle by foot-and-mouth disease virus (FMDV) infection and also following vaccination with inactivated FMDV.
3928 18272757 This study aimed to investigate major histocompatibility complex (MHC) class I-restricted CD8(+) T-cell responses to FMDV in vaccinated and in infected cattle.
3929 18272757 An in vitro assay was used to detect antigen-specific gamma interferon release by CD8(+) T cells in FMDV-infected cattle of known MHC class I genotypes.
3930 18272757 A significant MHC class I-restricted CD8(+) T-cell response was detected to both FMDV strain O1 BFS and a recombinant fowlpox virus expressing the structural proteins of FMDV.
3931 18272757 Antigen-specific MHC class I-restricted CD8(+) T-cell responses were also detected in cattle vaccinated with inactivated FMDV.
3932 18272757 An MHC-restricted CD8+ T-cell response is induced in cattle by foot-and-mouth disease virus (FMDV) infection and also following vaccination with inactivated FMDV.
3933 18272757 This study aimed to investigate major histocompatibility complex (MHC) class I-restricted CD8(+) T-cell responses to FMDV in vaccinated and in infected cattle.
3934 18272757 An in vitro assay was used to detect antigen-specific gamma interferon release by CD8(+) T cells in FMDV-infected cattle of known MHC class I genotypes.
3935 18272757 A significant MHC class I-restricted CD8(+) T-cell response was detected to both FMDV strain O1 BFS and a recombinant fowlpox virus expressing the structural proteins of FMDV.
3936 18272757 Antigen-specific MHC class I-restricted CD8(+) T-cell responses were also detected in cattle vaccinated with inactivated FMDV.
3937 18272757 An MHC-restricted CD8+ T-cell response is induced in cattle by foot-and-mouth disease virus (FMDV) infection and also following vaccination with inactivated FMDV.
3938 18272757 This study aimed to investigate major histocompatibility complex (MHC) class I-restricted CD8(+) T-cell responses to FMDV in vaccinated and in infected cattle.
3939 18272757 An in vitro assay was used to detect antigen-specific gamma interferon release by CD8(+) T cells in FMDV-infected cattle of known MHC class I genotypes.
3940 18272757 A significant MHC class I-restricted CD8(+) T-cell response was detected to both FMDV strain O1 BFS and a recombinant fowlpox virus expressing the structural proteins of FMDV.
3941 18272757 Antigen-specific MHC class I-restricted CD8(+) T-cell responses were also detected in cattle vaccinated with inactivated FMDV.
3942 18280180 The single-chain salmon MHC class I molecule has been designed and generated, in which the carboxyl terminus of beta2m is joined together with a flexible 15 or 20 amino acid peptide linker to the amino terminus of the heavy chain (Sasabeta2mUBA*0301).
3943 18292570 A significant proportion of T lymphocytes recognized M.Tb-CME (290 IFN-gamma+ T cells/10(5) PBMCs) and developed to effector memory cells as determined by the expression of CD45RO and the chemokine receptors CXCR3 and CCR5.
3944 18292570 Phenotypically, M.Tb-CME-expanded cells were CD4+ and MHC class II restricted, challenging current concepts that cytotoxic and antimicrobial effector cells are restricted to the CD8+ T cell subset.
3945 18321617 Studies on large AIDS cohorts and their meta-analyses have identified numerous AIDS restriction genes that regulate HIV cell entry (particularly chemokine co-receptors and their ligands), acquired and innate immunity (major histocompatibility complex (MHC), killer immunoglobulin-like receptors (KIRs), and cytokines) and others that influence outcome of HIV infection.
3946 18350542 Immunohistochemical studies revealed that CD11c+ MHC class II+ cells accumulated primarily in the colonic patches (CP) and lamina propria of the large intestine (LI-LP), iliac LN (ILN) and MLN following IR vaccination with CT.
3947 18353920 Phase I dose-escalation study of a monovalent heat shock protein 70-herpes simplex virus type 2 (HSV-2) peptide-based vaccine designed to prime or boost CD8 T-cell responses in HSV-naïve and HSV-2-infected subjects.
3948 18353920 This was a phase I study to assess the safety, tolerability, and immunogenicity of escalating doses of AG-702, a noncovalent complex of an HLA A*0201-restricted epitope in the glycoprotein B protein of herpes simplex virus type 2 (gB2) and truncated human constitutive heat shock protein 70.
3949 18354173 Assessment of Bet v 1-specific CD4+ T cell responses in allergic and nonallergic individuals using MHC class II peptide tetramers.
3950 18354173 In this study, we used HLA-DRB1*0101, DRB1*0401, and DRB1*1501 peptide tetramers combined with cytokine surface capture assays to characterize CD4(+) T cell responses against the immunodominant T cell epitope (peptide 141-155) from the major birch pollen allergen Bet v 1, in both healthy and allergic individuals.
3951 18354173 Analysis at a single-cell level revealed that allergen-specific CD4(+) T cells from healthy individuals secrete IFN-gamma and IL-10 in response to the allergen, whereas cells from allergic patients are bona fide Th2 cells (producing mostly IL-5, some IL-10, but no IFN-gamma), as corroborated by patterns of cytokines produced by T cell clones.
3952 18354173 A fraction of Bet v 1-specific cells isolated from healthy, but not allergic, individuals also expresses CTLA-4, glucocorticoid-induced TNF receptor, and Foxp 3, indicating that they represent regulatory T cells.
3953 18354221 Through an analysis of Ag uptake, activation of memory CD8 T cells, and display of peptide/MHC complex by DCs in draining LNs and spleen early after virus infection, we established that lack of protection is associated with defective Ag presentation by BM-derived DCs and defective homing of memory T cells in the lymph nodes draining the airway tract.
3954 18389062 Furthermore, M2 protein expression in primary murine B cells drives high level IL-10 expression along with increased secretion of IL-2, IL-6, and MIP-1alpha.
3955 18389062 M2 protein expression in primary B cells also led to upregulated surface expression of the high affinity IL-2 receptor (CD25) and the activation marker GL7, along with down-regulated surface expression of B220, MHC II, and sIgD.
3956 18390718 The amelioration of AIH was directly related to the induction of a specific population of flea antigenic specific T cells exhibiting a CD4(+)CD25(-)FoxP3(+) phenotype, a characteristic of regulatory T (T(REG)) cells.
3957 18390718 These T(REG) cells expressing IL-10, IFN-gamma, and the transcriptional factor T-bet after Ag stimulation were driven by a tolerogenic MHC class II(+)/CD40(low) dendritic cell population that was induced by the coimmunization of DNA and protein vaccines.
3958 18390718 The tolerogenic dendritic cell could educate the naive T cells into CD4(+)CD25(-)FoxP3(+) T(REG) cells both in vitro and in vivo.
3959 18398931 These results demonstrate preferential MHC class I and class II processing of cognate antigen incorporated in ISCOMS by specific B cells in vitro and in vivo, highlighting the ability of ISCOMS to target B cells and offering novel insights into the role of B cells in cross-presentation to CD8(+) T cells.
3960 18406420 To study the MHC class I antigen-processing pathway, the protein antigen of interest has to be expressed inside the cells.
3961 18406420 Mouse fibroblast and RMA cells were able to properly process OVA protein, and OVA-derived peptide OVA(258-265) (or SIINFEKL) was successfully presented via the MHC class I molecule (K(b)) to SIINFEKL-K(b)-specific T cell hybridoma B3Z.
3962 18406420 As expected, delivery of OVA protein into RMA-S, a cell line with a deficiency in MHC class I antigen processing due to a TAP defect, failed to present the SIINFEKL epitope to B3Z.
3963 18406420 To study the MHC class I antigen-processing pathway, the protein antigen of interest has to be expressed inside the cells.
3964 18406420 Mouse fibroblast and RMA cells were able to properly process OVA protein, and OVA-derived peptide OVA(258-265) (or SIINFEKL) was successfully presented via the MHC class I molecule (K(b)) to SIINFEKL-K(b)-specific T cell hybridoma B3Z.
3965 18406420 As expected, delivery of OVA protein into RMA-S, a cell line with a deficiency in MHC class I antigen processing due to a TAP defect, failed to present the SIINFEKL epitope to B3Z.
3966 18406420 To study the MHC class I antigen-processing pathway, the protein antigen of interest has to be expressed inside the cells.
3967 18406420 Mouse fibroblast and RMA cells were able to properly process OVA protein, and OVA-derived peptide OVA(258-265) (or SIINFEKL) was successfully presented via the MHC class I molecule (K(b)) to SIINFEKL-K(b)-specific T cell hybridoma B3Z.
3968 18406420 As expected, delivery of OVA protein into RMA-S, a cell line with a deficiency in MHC class I antigen processing due to a TAP defect, failed to present the SIINFEKL epitope to B3Z.
3969 18419256 The corresponding synthetic peptides (SP1 to SP3) were then tested for their abilities to induce proliferation of CD4 T cells isolated from five human volunteers screened positive for previous EV 71 exposure and one EV 71-negative volunteer.
3970 18419256 Moreover, CD4 T cells from EV 71-positive volunteers produced significant levels of IL-2 and IFN- upon stimulation, indicative of a T-cell differentiation into Th-1-type subset.
3971 18419256 Moreover, SP2-induced proliferative response could be inhibited with anti-major histocompatibility complex (MHC) class II antibody, indicating that SP2 represents a MHC class II-restricted CD4 T-cell epitope.
3972 18425453 To enhance MHC class II presentation of potential vaccine antigens, we have developed a method to target antigens for autophagic degradation via fusion to the Atg8/LC3 protein: Atg8/LC3 is specifically incorporated into autophagosomes via coupling to phosphatidylethanolamine, and subsequently degraded in MHC class II loading compartments (MIICs).
3973 18425453 Antigens fused to the N-terminus of Atg8/LC3 follow the same pathway and get preferentially presented on MHC class II molecules.
3974 18425453 The localization of Atg8/LC3 fusion antigens in MIICs can be visualized by confocal microscopy, and MHC class II presentation can be quantified in a presentation assay with antigen-specific CD4(+) T-cell clones.
3975 18425453 To enhance MHC class II presentation of potential vaccine antigens, we have developed a method to target antigens for autophagic degradation via fusion to the Atg8/LC3 protein: Atg8/LC3 is specifically incorporated into autophagosomes via coupling to phosphatidylethanolamine, and subsequently degraded in MHC class II loading compartments (MIICs).
3976 18425453 Antigens fused to the N-terminus of Atg8/LC3 follow the same pathway and get preferentially presented on MHC class II molecules.
3977 18425453 The localization of Atg8/LC3 fusion antigens in MIICs can be visualized by confocal microscopy, and MHC class II presentation can be quantified in a presentation assay with antigen-specific CD4(+) T-cell clones.
3978 18425453 To enhance MHC class II presentation of potential vaccine antigens, we have developed a method to target antigens for autophagic degradation via fusion to the Atg8/LC3 protein: Atg8/LC3 is specifically incorporated into autophagosomes via coupling to phosphatidylethanolamine, and subsequently degraded in MHC class II loading compartments (MIICs).
3979 18425453 Antigens fused to the N-terminus of Atg8/LC3 follow the same pathway and get preferentially presented on MHC class II molecules.
3980 18425453 The localization of Atg8/LC3 fusion antigens in MIICs can be visualized by confocal microscopy, and MHC class II presentation can be quantified in a presentation assay with antigen-specific CD4(+) T-cell clones.
3981 18427567 CD4+ T cells are required during priming but not the effector phase of antibody-mediated IFN-gamma-dependent protective immunity against pulmonary Francisella novicida infection.
3982 18427567 Intranasally vaccinated KKF24 C57BL/6 major histocompatibility class (MHC) class II-/- mice produced minimal antigen-specific interferon (IFN)-gamma and serum antibodies and were highly susceptible (0% survival) to F. novicida challenge, compared to MHC class I-/- or wild-type mice (both 100% survival).
3983 18427567 Taken together, our data indicate that CD4+ T cells are required for priming, but not during the effector phase, of anti-KKF24 antibody-mediated IFN-gamma-dependent immunity against pulmonary F. novicida infection.
3984 18434400 Significantly more HLA-B (chi(2); P = 3.59 x 10(-5)) and HLA-C (chi(2); P = 4.71 x 10(-6)) alleles were associated with amino acid changes than HLA-A, highlighting their importance in driving viral evolution.
3985 18450004 Studied alleles comprise HLA-A*0101, HLA-A*0201, HLA-A*0202, HLA-A*0203, HLA-A*0206, HLA-A*0301, HLA-A*1101, HLA-A*3101, HLA-A*6801, HLA-A*6802, HLA-B*3501, H2-K(k), H2-K(b), H2-D(b) HLA-DRB1*0101, HLA-DRB1*0401, HLA-DRB1*0701, I-A(b), I-A(d), I-A(k), I-A(S), I-E(d), and I-E(k).
3986 18450016 The transporter associated with antigen processing (TAP) plays a crucial role in the transport of the peptide fragments of the proteolysed antigenic or self-altered proteins to the endoplasmic reticulum where the association between these peptides and the major histocompatibility complex (MHC) class I molecules takes place.
3987 18453624 The MHC CIITA is a master regulator of MHC class II expression and also induces expression of class I molecules.
3988 18453624 Furthermore, our data suggested that coadministration of DNA-encoding calreticulin (CRT) linked to human papillomavirus (HPV) 16 E6 Ag (CRT/E6) with CIITA DNA leads to enhanced E6-specific CD8(+) T cell immune responses in vaccinated mice.
3989 18453624 In addition, coadministration of the combination of CRT/E6 DNA with CIITA DNA and DNA encoding the invariant chain (Ii) linked to the pan HLA-DR-reactive epitope (Ii-PADRE) further enhanced E6-specific CD8(+) T cell immune responses in vaccinated mice.
3990 18453624 Vaccination with the combination vaccine also led to enhanced E6-specific CD8(+) memory T cells and to long-term protection against TC-1 tumors and prolonged survival in vaccinated mice.
3991 18453624 Thus, our findings suggest that the combination of CIITA DNA with CRT/E6 and Ii-PADRE DNA vaccines represents a potentially effective means to combat tumors in the clinical setting.
3992 18479787 Therapeutic vaccination with dendritic cells pulsed with tumor-derived Hsp70 and a COX-2 inhibitor induces protective immunity against B16 melanoma.
3993 18479787 Here we sought to overcome this problem by therapeutic vaccination with dendritic cells (DC) pulsed with Hsp70 and a COX-2 inhibitor.
3994 18479787 We found that Hsp70 induces IL-6 and IL-10 production and suppressed expression of CD40 on DC.
3995 18479787 Incubation of DC with tumor-conditioned medium attenuated Hsp70-induced expression of CD80 and induced expression of COX-2.
3996 18479787 Inhibition of COX-2 partially reversed the stimulatory effect of Hsp70 on DC IL-6 and IL-10 production and enhanced expression of CD80 and MHC classes I and II.
3997 18479787 Therapeutic administration of DC pulsed in vitro with Hsp70 in the presence of a COX-2 inhibitor significantly reduced progression of B16 tumors in mice and significantly enhanced survival.
3998 18479787 This was associated with a reduction in the frequency of IL-10-producing CD4(+) T cells and enhancement of IFN-gamma-producing CD8(+) T cells.
3999 18479789 Cross-clade immune responses to Gag p24 in patients infected with different HIV-1 subtypes and correlation with HLA class I and II alleles.
4000 18481383 These results were translated in an in vivo therapeutic mouse model where humanized HLA-A(*)02.01 transgenic mice inoculated with EL-4/humanized HLA-A(*)02.01 transgenic mice showed a prolonged survival and the greatest rate of cure when receiving a combined treatment with a thymidylate synthase-specific peptide vaccine and a multidrug chemotherapy regimen administered late after immunization.
4001 18488218 DC engineered with AdV to express full length tumor antigens are capable stimulators of antigen-specific polyclonal CD8+ and CD4+ T cells.
4002 18488218 Statistically significant increases in expression were observed for peptide transporters TAP-1 and TAP-2, and HLA class I peptide-loading chaperone ERp57, as well as co-stimulatory surface molecule CD86 due to AdV transduction.
4003 18490718 First, CD8(+) T cell epitopes are not randomly distributed across the VACV proteome, with some proteins being poorly or nonimmunogenic, while others are immunoprevalent, being frequently recognized across diverse MHC haplotypes.
4004 18490718 Together, these findings have clear implications for the design of CD8(+) T cell subunit vaccines and in particular raise the exciting prospect of being able to choose subunits without reference to MHC restriction.
4005 18490718 First, CD8(+) T cell epitopes are not randomly distributed across the VACV proteome, with some proteins being poorly or nonimmunogenic, while others are immunoprevalent, being frequently recognized across diverse MHC haplotypes.
4006 18490718 Together, these findings have clear implications for the design of CD8(+) T cell subunit vaccines and in particular raise the exciting prospect of being able to choose subunits without reference to MHC restriction.
4007 18491093 One type of metastases characterized by upregulation of all MHC class I antigens and another type with partial IFN-gamma resistance, namely with lack of expression of L(d)-MHC class I molecule.
4008 18501999 High-resolution phenotypes of human leukocyte antigen (HLA)-A, -B, and -DRB1 loci were determined by sequence-specific oligonucleotide probe hybridization.
4009 18502835 We evaluated WT1 as an immunotherapeutic target using our proven DNA fusion vaccine design, p.DOM-peptide, encoding a minimal tumor-derived major histocompatibility complex (MHC) class I-binding epitope downstream of a foreign sequence of tetanus toxin.
4010 18523278 CTLs directed against HER2 specifically cross-react with HER3 and HER4.
4011 18523278 The human epidermal growth factor receptor 2 (HER2) has been targeted as a breast cancer-associated Ag by T cell-based immunotherapeutical strategies such as cancer vaccines and adoptive T cell transfer.
4012 18523278 In this study, we generated human cytotoxic T cell clones directed against the HER2(369-377) epitope known to be naturally presented with HLA-A*0201.
4013 18523278 Several HER2-expressing tumor cells became susceptible to CTL-mediated lysis after IFN-gamma treatment and, in parallel, up-regulated molecules of the Ag-presenting machinery, indicating that the tumor itself also contributes to the success of CTL-mediated killing.
4014 18541714 An MHC class Ib-restricted CD8 T cell response confers antiviral immunity.
4015 18541714 Although immunity against intracellular pathogens is primarily provided by CD8 T lymphocytes that recognize pathogen-derived peptides presented by major histocompatibility complex (MHC) class Ia molecules, MHC class Ib-restricted CD8 T cells have been implicated in antiviral immunity.
4016 18541714 We identified the ligand for PyV-specific CD8 T cells in K(b-/-)D(b-/-) mice as a nonamer peptide from the VP2 capsid protein presented by Q9, a member of the beta(2) microglobulin-associated Qa-2 family.
4017 18541714 To our knowledge, this is the first evidence for a defined MHC class Ib-restricted antiviral CD8 T cell response that contributes to host defense.
4018 18541714 This study motivates efforts to uncover MHC class Ib-restricted CD8 T cell responses in other viral infections, and given the limited polymorphism of MHC class Ib molecules, it raises the possibility of developing peptide-based viral vaccines having broad coverage across MHC haplotypes.
4019 18541714 An MHC class Ib-restricted CD8 T cell response confers antiviral immunity.
4020 18541714 Although immunity against intracellular pathogens is primarily provided by CD8 T lymphocytes that recognize pathogen-derived peptides presented by major histocompatibility complex (MHC) class Ia molecules, MHC class Ib-restricted CD8 T cells have been implicated in antiviral immunity.
4021 18541714 We identified the ligand for PyV-specific CD8 T cells in K(b-/-)D(b-/-) mice as a nonamer peptide from the VP2 capsid protein presented by Q9, a member of the beta(2) microglobulin-associated Qa-2 family.
4022 18541714 To our knowledge, this is the first evidence for a defined MHC class Ib-restricted antiviral CD8 T cell response that contributes to host defense.
4023 18541714 This study motivates efforts to uncover MHC class Ib-restricted CD8 T cell responses in other viral infections, and given the limited polymorphism of MHC class Ib molecules, it raises the possibility of developing peptide-based viral vaccines having broad coverage across MHC haplotypes.
4024 18541714 An MHC class Ib-restricted CD8 T cell response confers antiviral immunity.
4025 18541714 Although immunity against intracellular pathogens is primarily provided by CD8 T lymphocytes that recognize pathogen-derived peptides presented by major histocompatibility complex (MHC) class Ia molecules, MHC class Ib-restricted CD8 T cells have been implicated in antiviral immunity.
4026 18541714 We identified the ligand for PyV-specific CD8 T cells in K(b-/-)D(b-/-) mice as a nonamer peptide from the VP2 capsid protein presented by Q9, a member of the beta(2) microglobulin-associated Qa-2 family.
4027 18541714 To our knowledge, this is the first evidence for a defined MHC class Ib-restricted antiviral CD8 T cell response that contributes to host defense.
4028 18541714 This study motivates efforts to uncover MHC class Ib-restricted CD8 T cell responses in other viral infections, and given the limited polymorphism of MHC class Ib molecules, it raises the possibility of developing peptide-based viral vaccines having broad coverage across MHC haplotypes.
4029 18541714 An MHC class Ib-restricted CD8 T cell response confers antiviral immunity.
4030 18541714 Although immunity against intracellular pathogens is primarily provided by CD8 T lymphocytes that recognize pathogen-derived peptides presented by major histocompatibility complex (MHC) class Ia molecules, MHC class Ib-restricted CD8 T cells have been implicated in antiviral immunity.
4031 18541714 We identified the ligand for PyV-specific CD8 T cells in K(b-/-)D(b-/-) mice as a nonamer peptide from the VP2 capsid protein presented by Q9, a member of the beta(2) microglobulin-associated Qa-2 family.
4032 18541714 To our knowledge, this is the first evidence for a defined MHC class Ib-restricted antiviral CD8 T cell response that contributes to host defense.
4033 18541714 This study motivates efforts to uncover MHC class Ib-restricted CD8 T cell responses in other viral infections, and given the limited polymorphism of MHC class Ib molecules, it raises the possibility of developing peptide-based viral vaccines having broad coverage across MHC haplotypes.
4034 18566327 Here we characterized CD8(+) T-cell activity against beta-galactosidase and enhanced green fluorescent protein, model antigens containing major histocompatibility complex (MHC) class I epitopes that are constitutively produced in murine skeletal muscle after rAAV vector transduction.
4035 18566379 Identification of a novel immunogenic HLA-A*0201-binding epitope of HER-2/neu with potent antitumor properties.
4036 18566379 By applying prediction algorithms for MHC class I ligands and proteosomal cleavages, in this study, we describe the identification of HER-2/neu decamer LIAHNQVRQV spanning residues 85-94 (HER-2(10(85))).
4037 18566379 This peptide was immunogenic in HLA-A2.1 transgenic (HHD) mice inducing peptide-specific CTL, which responded to tumor cell lines of various origin coexpressing human HER-2/neu and HLA-A2.1.
4038 18566379 Five of sixteen HER-2/neu+ HLA-A2.1+ breast cancer patients analyzed had HER-2(10(85))-reactive T cells ranging from 0.35-0.70% of CD8+ T cells.
4039 18566379 Depletion of T regulatory cells from PBMC enabled the rapid expansion of HLA-A2.1/HER-2(10(85))pentamer+/CD8+ cells (PENT+/CD8+), whereas significantly lower numbers of CTL could be generated from unfractionated PBMC.
4040 18566379 HER-2(10(85))-specific human CTL recognized the HER-2/neu+ HLA-A2.1+ tumor cell line SKBR3.A2, as determined by IFN-gamma intracellular staining and in the high sensitivity CD107alpha degranulation assay.
4041 18566379 These data demonstrate that HER-2(10(85)) is an immunogenic peptide, capable of eliciting CD8-mediated responses in vitro and in vivo, providing the platform for further exploitation of HER-2(10(85)) as a possible target for anticancer immunotherapy.
4042 18566379 Identification of a novel immunogenic HLA-A*0201-binding epitope of HER-2/neu with potent antitumor properties.
4043 18566379 By applying prediction algorithms for MHC class I ligands and proteosomal cleavages, in this study, we describe the identification of HER-2/neu decamer LIAHNQVRQV spanning residues 85-94 (HER-2(10(85))).
4044 18566379 This peptide was immunogenic in HLA-A2.1 transgenic (HHD) mice inducing peptide-specific CTL, which responded to tumor cell lines of various origin coexpressing human HER-2/neu and HLA-A2.1.
4045 18566379 Five of sixteen HER-2/neu+ HLA-A2.1+ breast cancer patients analyzed had HER-2(10(85))-reactive T cells ranging from 0.35-0.70% of CD8+ T cells.
4046 18566379 Depletion of T regulatory cells from PBMC enabled the rapid expansion of HLA-A2.1/HER-2(10(85))pentamer+/CD8+ cells (PENT+/CD8+), whereas significantly lower numbers of CTL could be generated from unfractionated PBMC.
4047 18566379 HER-2(10(85))-specific human CTL recognized the HER-2/neu+ HLA-A2.1+ tumor cell line SKBR3.A2, as determined by IFN-gamma intracellular staining and in the high sensitivity CD107alpha degranulation assay.
4048 18566379 These data demonstrate that HER-2(10(85)) is an immunogenic peptide, capable of eliciting CD8-mediated responses in vitro and in vivo, providing the platform for further exploitation of HER-2(10(85)) as a possible target for anticancer immunotherapy.
4049 18585419 The aim of this research was to identify subunit immunogens that can generate enhanced CD8 T cell and TH1 responses against Mycobacterium tuberculosis.
4050 18585419 To further enhance the CD8 T cell and TH1 responses, a hybrid protein, H32, was constructed by combining the nucleotide sequences encoding the MHC class I antigen-rich segment of Rv1986c and the entire Rv3875 sequence.
4051 18591381 Using optimized culture conditions and HLA-A*02-restricted PRAME-peptides, we have consistently generated PRAME CTLs from 8/9 healthy donors and 5/6 CML patients.
4052 18591381 These CTLs released IFNgamma in response to PRAME peptides (between 113 +/- 8 and 795 +/- 23 spot forming cells/10(5) T cells) and lysed PRAME peptide-loaded cells (45 +/- 19% at an effector:target [E:T] ratio of 20:1) in a MHC-restricted fashion.
4053 18591381 Importantly, these CTLs recognized and had cytotoxic activity against HLA-A*02(+)/PRAME(+) tumor cell lines, and could recognize and respond to primary CML cells.
4054 18591381 Using optimized culture conditions and HLA-A*02-restricted PRAME-peptides, we have consistently generated PRAME CTLs from 8/9 healthy donors and 5/6 CML patients.
4055 18591381 These CTLs released IFNgamma in response to PRAME peptides (between 113 +/- 8 and 795 +/- 23 spot forming cells/10(5) T cells) and lysed PRAME peptide-loaded cells (45 +/- 19% at an effector:target [E:T] ratio of 20:1) in a MHC-restricted fashion.
4056 18591381 Importantly, these CTLs recognized and had cytotoxic activity against HLA-A*02(+)/PRAME(+) tumor cell lines, and could recognize and respond to primary CML cells.
4057 18591381 Using optimized culture conditions and HLA-A*02-restricted PRAME-peptides, we have consistently generated PRAME CTLs from 8/9 healthy donors and 5/6 CML patients.
4058 18591381 These CTLs released IFNgamma in response to PRAME peptides (between 113 +/- 8 and 795 +/- 23 spot forming cells/10(5) T cells) and lysed PRAME peptide-loaded cells (45 +/- 19% at an effector:target [E:T] ratio of 20:1) in a MHC-restricted fashion.
4059 18591381 Importantly, these CTLs recognized and had cytotoxic activity against HLA-A*02(+)/PRAME(+) tumor cell lines, and could recognize and respond to primary CML cells.
4060 18598189 Accordingly, in infants hospitalized with acute dengue, the activation phenotype of peripheral-blood NK cells and CD8+ and CD4+ T cells correlated with overall disease severity, but HLA-A*1101-restricted NS3(133-142)-specific CD8+ T cells were not measurable until early convalescence.
4061 18645033 We identified three novel mouse TH (mTH3) derived peptides with high predicted binding affinity to MHC class I antigen H2-K(k) according to the prediction program SYFPEITHI and computer modeling of epitopes into the MHC class I antigen binding groove.
4062 18645033 This effect was clearly dependent on ubiquitin and high affinity of the mTH epitopes to MHC class I antigens.
4063 18645033 We identified three novel mouse TH (mTH3) derived peptides with high predicted binding affinity to MHC class I antigen H2-K(k) according to the prediction program SYFPEITHI and computer modeling of epitopes into the MHC class I antigen binding groove.
4064 18645033 This effect was clearly dependent on ubiquitin and high affinity of the mTH epitopes to MHC class I antigens.
4065 18713977 It has been demonstrated that CD4(+) T cells require Ag persistence to achieve effective priming, whereas CD8(+) T cells are on "autopilot" after only a brief exposure.
4066 18713977 This finding presents a disturbing conundrum as it does not account for situations in which CD8(+) T cells require CD4(+) T cell help.
4067 18713977 In fact, by providing "extra help" in the form of dendritic cells (DCs) loaded with MHC class II peptide, it was possible to achieve robust activation of CD8(+) T cells.
4068 18713977 Our data suggest that the "licensing" of cross-presenting DCs does not occur during their initial encounter with CD4(+) T cells, thus accounting for the requirement for Ag persistence and suggesting that DCs make multiple interactions with CD8(+) T cells during the priming phase.
4069 18713974 In this study, we present evidence that the selectivity of CD4 T cell responses to peptides contained within protein Ags is not detectably influenced by the location of the peptide in a given protein or the primary sequence of the protein that bears the test peptide.
4070 18713974 Collectively, these results suggest immunodominance of peptides contained in complex Ags is due to an intrinsic factor of the peptide, based upon the affinity of that peptide for MHC class II molecules.
4071 18726439 After DNA transfection, the epitope minigenes were expressed respectively in two human cell lines, each bearing one MHC class I molecule named CIR/HLA-A2.1 and K562/HLA-B51.
4072 18773115 Mutations in human leukocyte antigen (HLA) class I-restricted epitopes targeted by CD8(+) T cells are associated with persistence, but the extent to which these mutations affect viral fitness is not fully understood.
4073 18781830 Abstract The development of tumor vaccines or generation of tumor-specific cytotoxic T lymphocytes (CTL) is limited by the fact that many tumor cells downregulate the expression of major histocompatibility complex (MHC) Class I and II molecules, as well as key co-stimulatory molecules such as CD80 and CD86.
4074 18781830 The resulting hybridoma cells expressed the neural antigen GD2 as well as MHC Class I, Class II, CD 80, and CD86.
4075 18781830 Abstract The development of tumor vaccines or generation of tumor-specific cytotoxic T lymphocytes (CTL) is limited by the fact that many tumor cells downregulate the expression of major histocompatibility complex (MHC) Class I and II molecules, as well as key co-stimulatory molecules such as CD80 and CD86.
4076 18781830 The resulting hybridoma cells expressed the neural antigen GD2 as well as MHC Class I, Class II, CD 80, and CD86.
4077 18791162 The uncleaved 12-kDa form of p12(I) resides in the ER and interacts with the beta and gamma(c) chains of the interleukin-2 receptor (IL-2R), the heavy chain of the major histocompatibility complex (MHC) class I, as well as calreticulin and calnexin.
4078 18809757 Clinical responses were significantly associated with a reduction in CD4(+)CD25(+)FOXP3(+) regulatory T cells, an increase in CD3(-)CD56(dim)CD16(+) natural killer (NK) cells, and maturation of lymphocytes to the effector memory stage in either postvaccination peripheral blood or tumor specimen samples.
4079 18809757 In one HLA-A*0201(+) patient who achieved CR, IL-4 release by circulating T cells in response to tumor-specific IgH-encoded peptides was also documented.
4080 18820911 HER-2/neu mediated down-regulation of MHC class I antigen processing prevents CTL-mediated tumor recognition upon DNA vaccination in HLA-A2 transgenic mice.
4081 18820911 Subsequently we discovered that HER-2 transfected tumor cells down-regulated MHC class I antigen expression and exhibited a series of defects in the antigen processing pathway which impaired the capacity to produce and display MHC class I peptide-ligands to specific CTLs.
4082 18820911 Our data demonstrate that HER-2 transfection is associated with defects in the MHC class I presentation pathway, which may be the underlying mechanism behind the inability of CTLs to recognize tumors in this HLA-A2 transgenic model.
4083 18820911 As defective MHC class I presentation may be a common characteristic of HER-2 expressing tumors, vaccines targeting HER-2 should aim at inducing an integrated immune response where also CD4(+) T cells and antibodies are important components.
4084 18820911 HER-2/neu mediated down-regulation of MHC class I antigen processing prevents CTL-mediated tumor recognition upon DNA vaccination in HLA-A2 transgenic mice.
4085 18820911 Subsequently we discovered that HER-2 transfected tumor cells down-regulated MHC class I antigen expression and exhibited a series of defects in the antigen processing pathway which impaired the capacity to produce and display MHC class I peptide-ligands to specific CTLs.
4086 18820911 Our data demonstrate that HER-2 transfection is associated with defects in the MHC class I presentation pathway, which may be the underlying mechanism behind the inability of CTLs to recognize tumors in this HLA-A2 transgenic model.
4087 18820911 As defective MHC class I presentation may be a common characteristic of HER-2 expressing tumors, vaccines targeting HER-2 should aim at inducing an integrated immune response where also CD4(+) T cells and antibodies are important components.
4088 18820911 HER-2/neu mediated down-regulation of MHC class I antigen processing prevents CTL-mediated tumor recognition upon DNA vaccination in HLA-A2 transgenic mice.
4089 18820911 Subsequently we discovered that HER-2 transfected tumor cells down-regulated MHC class I antigen expression and exhibited a series of defects in the antigen processing pathway which impaired the capacity to produce and display MHC class I peptide-ligands to specific CTLs.
4090 18820911 Our data demonstrate that HER-2 transfection is associated with defects in the MHC class I presentation pathway, which may be the underlying mechanism behind the inability of CTLs to recognize tumors in this HLA-A2 transgenic model.
4091 18820911 As defective MHC class I presentation may be a common characteristic of HER-2 expressing tumors, vaccines targeting HER-2 should aim at inducing an integrated immune response where also CD4(+) T cells and antibodies are important components.
4092 18820911 HER-2/neu mediated down-regulation of MHC class I antigen processing prevents CTL-mediated tumor recognition upon DNA vaccination in HLA-A2 transgenic mice.
4093 18820911 Subsequently we discovered that HER-2 transfected tumor cells down-regulated MHC class I antigen expression and exhibited a series of defects in the antigen processing pathway which impaired the capacity to produce and display MHC class I peptide-ligands to specific CTLs.
4094 18820911 Our data demonstrate that HER-2 transfection is associated with defects in the MHC class I presentation pathway, which may be the underlying mechanism behind the inability of CTLs to recognize tumors in this HLA-A2 transgenic model.
4095 18820911 As defective MHC class I presentation may be a common characteristic of HER-2 expressing tumors, vaccines targeting HER-2 should aim at inducing an integrated immune response where also CD4(+) T cells and antibodies are important components.
4096 18941228 Viral peptides are presented by HLA class I on infected cells to activate CD8(+) T cells.
4097 18941228 We describe 12 viral peptides presented by HLA-A*0201 and 3 by HLA-B*0702.
4098 18941228 Viral peptides are presented by HLA class I on infected cells to activate CD8(+) T cells.
4099 18941228 We describe 12 viral peptides presented by HLA-A*0201 and 3 by HLA-B*0702.
4100 18945465 We demonstrated that VLP expressed by recombinant baculoviruses activate human PBMC to release pro-inflammatory (lL-6, TNF-alpha), anti-inflammatory (IL-10) and Th1-polarizing (IFN-gamma) cytokines as well as GM-CSF and MIP-1alpha in a dose-and time-dependent manner.
4101 18945465 Furthermore, VLP-induced monocyte activation was shown by upregulation of molecules involved in antigen presentation (MHC II, CD80, CD86) and cell adhesion (CD54).
4102 18977266 We studied the levels of expression of interleukin 1beta (IL-1beta), major histocompatibility complex (MHC) class Ialpha and IIalpha genes, immunoglobulin M (IgM), CD8alpha, type I interferon (IFN), Mx, IFN-gamma and natural killer enhancing factor (NKEF) in head kidney, spleen and blood.
4103 18977266 When we compared the effect that VHSV had on vaccinated fish to the effect that the virus produced in fish vaccinated with the empty plasmid, the genes that were significantly up-regulated were IL-1beta and MHC IIalpha in the spleen at day 1 post-infection, MHC Ialpha in all organs at day 1 post-infection, and IFN and Mx in the spleen and blood at days 1 and 3 post-infection, respectively.
4104 18977266 We studied the levels of expression of interleukin 1beta (IL-1beta), major histocompatibility complex (MHC) class Ialpha and IIalpha genes, immunoglobulin M (IgM), CD8alpha, type I interferon (IFN), Mx, IFN-gamma and natural killer enhancing factor (NKEF) in head kidney, spleen and blood.
4105 18977266 When we compared the effect that VHSV had on vaccinated fish to the effect that the virus produced in fish vaccinated with the empty plasmid, the genes that were significantly up-regulated were IL-1beta and MHC IIalpha in the spleen at day 1 post-infection, MHC Ialpha in all organs at day 1 post-infection, and IFN and Mx in the spleen and blood at days 1 and 3 post-infection, respectively.
4106 18989404 Although their structure confirms the similarity of CD1 proteins to MHC class I and class II antigen presenting molecules, the mCD1d groove is relatively narrow, deep, and highly hydrophobic and it has two binding pockets instead of the several shallow pockets described for the classical MHC-encoded antigen-presenting molecules.
4107 19008459 Toward this end, we screened a murine renal cell carcinoma cDNA expression library with sera from mice vaccinated with irradiated tumor cells engineered to secrete granulocyte macrophage colony-stimulating factor (GM-CSF).
4108 19008459 High titer antibodies to human PDI were similarly induced in an acute myeloid leukemia patient who achieved a complete response after vaccination with irradiated, autologous GM-CSF-secreting tumor cells in the setting of nonmyeloablative allogeneic bone marrow transplantation.
4109 19008459 Moreover, ERp5, a closely related disulfide isomerase involved in major histocompatibility complex (MHC) class I chain-related protein A (MICA) shedding, also evoked potent humoral reactions in diverse solid and hematologic malignancy patients who responded to GM-CSF-secreting tumor cell vaccines or antibody blockade of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4).
4110 19010918 First, we showed that rat KDC have an MHC II(+)CD103(+)CD11b(+)NKp46(-) phenotype and are therefore distinct from natural killer cells, which are MHC II(-)CD103(-)CD11b(-)NKp46(+).
4111 19036499 MHC independent anti-tumor immune responses induced by Hsp70-enriched exosomes generate tumor regression in murine models.
4112 19036499 Tumor-derived exosomes are small membrane vesicles containing tumor antigens as well as other immunologically important molecules such as MHC molecules and heat shock proteins (HSPs).
4113 19036499 MHC independent anti-tumor immune responses induced by Hsp70-enriched exosomes generate tumor regression in murine models.
4114 19036499 Tumor-derived exosomes are small membrane vesicles containing tumor antigens as well as other immunologically important molecules such as MHC molecules and heat shock proteins (HSPs).
4115 19036810 Protective HLA class I alleles that restrict acute-phase CD8+ T-cell responses are associated with viral escape mutations located in highly conserved regions of human immunodeficiency virus type 1.
4116 19036810 The control of human immunodeficiency virus type 1 (HIV-1) associated with particular HLA class I alleles suggests that some CD8(+) T-cell responses may be more effective than others at containing HIV-1.
4117 19036810 To address this hypothesis at the population level, we derived near-full-length viral genomes from 98 chronically infected individuals and identified a total of 76 HLA class I-associated mutations across the genome, reflective of CD8 responses capable of selecting for sequence evolution.
4118 19036810 Protective HLA class I alleles that restrict acute-phase CD8+ T-cell responses are associated with viral escape mutations located in highly conserved regions of human immunodeficiency virus type 1.
4119 19036810 The control of human immunodeficiency virus type 1 (HIV-1) associated with particular HLA class I alleles suggests that some CD8(+) T-cell responses may be more effective than others at containing HIV-1.
4120 19036810 To address this hypothesis at the population level, we derived near-full-length viral genomes from 98 chronically infected individuals and identified a total of 76 HLA class I-associated mutations across the genome, reflective of CD8 responses capable of selecting for sequence evolution.
4121 19036810 Protective HLA class I alleles that restrict acute-phase CD8+ T-cell responses are associated with viral escape mutations located in highly conserved regions of human immunodeficiency virus type 1.
4122 19036810 The control of human immunodeficiency virus type 1 (HIV-1) associated with particular HLA class I alleles suggests that some CD8(+) T-cell responses may be more effective than others at containing HIV-1.
4123 19036810 To address this hypothesis at the population level, we derived near-full-length viral genomes from 98 chronically infected individuals and identified a total of 76 HLA class I-associated mutations across the genome, reflective of CD8 responses capable of selecting for sequence evolution.
4124 19042022 However, upon immunization, the H164V APL considerably downregulated proliferation and cytokine responses to the wild type LACK 161-175 peptide, while immunization with the weak agonist, MHC contact APL S171K, increased the IFN-gamma/IL-4 ratio to the wild type peptide.
4125 19053208 Invariant natural killer T (iNKT) cells are a unique subset of T lymphocytes that recognize glycolipid antigens in the context of the antigen-presenting molecule CD1d.
4126 19054057 In this study, we showed the importance of antigen presentation via a major histocompatibility complex (MHC) class II molecule in cancer immunity against non-membrane bound TAAs such as the melanoma antigen gp100 by using DCs derived from MHC class II-deficient mice (C2KO).
4127 19075652 Based on the analysis of anchor residues that were important for the interaction between peptides and HLA class I molecules, WT1 cytotoxic T lymphocyte (CTL) epitopes with the restriction of HLA-A 0201 and HLA-A 2402 were identified, and clinical trials of WT1 peptide vaccination for cancer patients with these HLA class I types were started.
4128 19079589 Thirteen WT1 peptides sequences were synthesized with chemically modified amino acids (via fluorination and photo-reactive group additions) at MHC and T cell receptor binding positions.
4129 19109450 We measured the activation of the antigen-presenting major histocompatibility complex (MHC) class II molecule, costimulatory molecules CD40 and CD86, the cytokine interleukin-12 (IL-12), and the transcriptional factor interferon regulatory factor 1 (IRF-1) in monocyte-derived macrophages (mMOs) and dendritic cells (mDCs) of adult horses and foals of different ages (from birth to 3 months of age) infected with virulent R. equi or its avirulent, plasmid-cured derivative.
4130 19109450 R. equi infection promoted comparable expression of costimulatory molecules CD86 and CD40 in foal and adult horse cells.
4131 19110021 We demonstrate for the first time that treatment with yeast-CEA can activate human DCs, resulting in increases in surface expression of CD80, CD83, CD54, CD58, and MHC class II, and increased production by DCs of IL-12p70, TNF-alpha, IFN-gamma, IL-8, IL-2, IL-13, IL-10, and IL-1beta.
4132 19131115 Beta-defensin 129, T-cell surface glycoprotein CD8 and B-cell receptor-associated protein 29 were overexpressed in infected animals.
4133 19131115 Lower expression levels of the immune response genes galectin-1, complement component C1qB and certain HLA class I and class II histocompatibility antigens and immunoglobulin chains were found in infected animals.
4134 19148489 Capability of SART3(109-118) peptide to induce cytotoxic T lymphocytes from prostate cancer patients with HLA class I-A11, -A31 and -A33 alleles.
4135 19148489 IgG reactive to SART3(109-118) peptide was identified in sera of the vast majority of non-cancer subjects (n=50) and all cancer patients (n=50) tested without apparent HLA-A association.
4136 19148489 Capability of SART3(109-118) peptide to induce cytotoxic T lymphocytes from prostate cancer patients with HLA class I-A11, -A31 and -A33 alleles.
4137 19148489 IgG reactive to SART3(109-118) peptide was identified in sera of the vast majority of non-cancer subjects (n=50) and all cancer patients (n=50) tested without apparent HLA-A association.
4138 19157553 By lengthening previously defined T cell epitopes by central amino acid insertion, we demonstrate that the peptide length specificity of some common HLA class I alleles (HLA-B*3501, B*0702 and A*2402) is very broad, and includes peptides of up to 25 residues.
4139 19178136 Molecular mechanisms of MHC class I-antigen processing: redox considerations.
4140 19178136 Major histocompatibility complex (MHC) class I molecules present antigenic peptides to the cell surface for screening by CD8(+) T cells.
4141 19178136 Early folding of the MHC class I heavy chain is followed by its association with beta(2)-microglobulin (beta(2)m).
4142 19178136 Molecular mechanisms of MHC class I-antigen processing: redox considerations.
4143 19178136 Major histocompatibility complex (MHC) class I molecules present antigenic peptides to the cell surface for screening by CD8(+) T cells.
4144 19178136 Early folding of the MHC class I heavy chain is followed by its association with beta(2)-microglobulin (beta(2)m).
4145 19178136 Molecular mechanisms of MHC class I-antigen processing: redox considerations.
4146 19178136 Major histocompatibility complex (MHC) class I molecules present antigenic peptides to the cell surface for screening by CD8(+) T cells.
4147 19178136 Early folding of the MHC class I heavy chain is followed by its association with beta(2)-microglobulin (beta(2)m).
4148 19215191 A multi-DNA preventive vaccine for p53/Neu-driven cancer syndrome.
4149 19215191 The highly aggressive cancer syndrome of female mice carrying a p53 knockout allele and a rat HER-2/neu (Neu) transgene (BALB-p53Neu) can be prevented by a cell vaccine presenting three components: Neu, interleukin (IL)-12 production, and allogeneic major histocompatibility complex (MHC) alleles (Triplex cell vaccine).
4150 19215191 Here we tested a second-generation Triplex DNA-based vaccine (Tri-DNA), consisting of the combination of three gene components (a transmembrane-extracellular domain fragment of the Neu gene, IL-12 genes, and the H-2D(q) allogeneic MHC gene), carried by separate plasmids.
4151 19215191 A multi-DNA preventive vaccine for p53/Neu-driven cancer syndrome.
4152 19215191 The highly aggressive cancer syndrome of female mice carrying a p53 knockout allele and a rat HER-2/neu (Neu) transgene (BALB-p53Neu) can be prevented by a cell vaccine presenting three components: Neu, interleukin (IL)-12 production, and allogeneic major histocompatibility complex (MHC) alleles (Triplex cell vaccine).
4153 19215191 Here we tested a second-generation Triplex DNA-based vaccine (Tri-DNA), consisting of the combination of three gene components (a transmembrane-extracellular domain fragment of the Neu gene, IL-12 genes, and the H-2D(q) allogeneic MHC gene), carried by separate plasmids.
4154 19225081 We designed a novel MHC class II molecule-peptide microarray binding assay and evaluated 346 peptides from already identified human immunodeficiency virus (HIV) epitopes and an additional set (n = 206) of 20-mer peptides, overlapping by 15 amino acid residues, from HIV type 1B (HIV-1B) gp160 and Nef as a paradigm.
4155 19225081 MHC class II binding peptides reside within previously described immunogenic regions of HIV gp160 and Nef, yet we could also identify new MHC class II binding peptides from gp160 and Nef.
4156 19225081 We designed a novel MHC class II molecule-peptide microarray binding assay and evaluated 346 peptides from already identified human immunodeficiency virus (HIV) epitopes and an additional set (n = 206) of 20-mer peptides, overlapping by 15 amino acid residues, from HIV type 1B (HIV-1B) gp160 and Nef as a paradigm.
4157 19225081 MHC class II binding peptides reside within previously described immunogenic regions of HIV gp160 and Nef, yet we could also identify new MHC class II binding peptides from gp160 and Nef.
4158 19235768 This unit describes a cDNA expression system and a genetic targeting expression system for the cloning of genes encoding for MHC class I- and II-restricted antigens recognized by antigen-specific CD8(+) and CD4(+) T cells.
4159 19238199 Here we used inverse folding approach to study the peptide specificity of MHC Class-I molecule with the aim of obtaining a better differentiation between binding and nonbinding sequence.
4160 19254781 We disrupted regulatory T cell (Treg) function to probe the balance between breast cancer vaccination and autoimmune thyroiditis (EAT) in four models, with particular attention to MHC-associated susceptibility, EAT induction with mouse thyroglobulin (mTg) without adjuvant, and tolerance to Her-2/neu in transgenic mice. 1) In EAT-resistant BALB/c mice, Treg depletion enhanced tumor regression, and facilitated mild thyroiditis induction. 2) In Her-2 tolerant C57BL/6 mice expressing HLA-DR3, an EAT-susceptibility allele, Her-2 DNA vaccinations must follow Treg depletion for (Her-2xDR3)F(1) mice to resist tumor challenge; thyroiditis incidence was moderated by the EAT-resistant IA(b) allele. 3) In neu tolerant, EAT-resistant BALB/c mice, implanted neu(+) tumor also regressed only after Treg depletion and DNA vaccinations.
4161 19254781 In all three, immune stimuli from concurrent tumor regression and EAT development have a noticeable, mutually augmenting effect. 4) In Treg-depleted, EAT-susceptible CBA/J mice, strong tumor protection was established by immunization with a cell vaccine. mTg injections led to greater thyroiditis incidence and severity.
4162 19330328 We previously reported peptide vaccine candidates for HLA-A3 supertype (-A3, -A11, -A31, -A33)-positive cancer patients.
4163 19330328 Among these peptides, one from the prostate acid phosphatase protein exhibited binding activity to HLA-A*0201, -A*0206, and -A*2402 molecules.
4164 19339351 Based on haplotype frequency, we hypothesized that CD8(+) T-cell responses restricted by these MHC class I alleles would be detected in nearly all MCM.
4165 19444908 In this study, we generated human T lymphocytes directed against the immunodominant NY-ESO-1(157-165) epitope known to be naturally presented with HLA-A*0201.
4166 19539989 To assess the immune response, cell surface markers including MHC II, CD86, CD40, and CD209 and cytokines including IL-6, IL-12p40, and IL-10 were measured.
4167 19557412 Uveal melanoma cell-based vaccines express MHC II molecules that traffic via the endocytic and secretory pathways and activate CD8+ cytotoxic, tumor-specific T cells.
4168 19557412 MHC II uveal melanoma vaccines are MHC class I(+) uveal melanoma cells transduced with CD80 genes and MHC II genes syngeneic to the recipient.
4169 19557412 We also demonstrate that uveal melanoma MHC II vaccines activate uveal melanoma-specific, cytolytic CD8(+) T cells that do not lyse normal fibroblasts or other tumor cells.
4170 19557412 Surprisingly, the CD8(+) T cells are cytolytic for HLA-A syngeneic and MHC I-mismatched uveal melanomas.
4171 19557412 Collectively, these studies demonstrate that MHC II uveal melanoma vaccines are potent activators of tumor-specific CD4(+) and CD8(+) T cells and suggest that the non-conventional intracellular trafficking pattern of MHC II may contribute to their enhanced immunogenicity.
4172 19557412 Since MHC I compatibility is unnecessary for the activation of cytolytic CD8(+) T cells, the vaccines could be used in uveal melanoma patients without regard to MHC I genotype.
4173 19557412 Uveal melanoma cell-based vaccines express MHC II molecules that traffic via the endocytic and secretory pathways and activate CD8+ cytotoxic, tumor-specific T cells.
4174 19557412 MHC II uveal melanoma vaccines are MHC class I(+) uveal melanoma cells transduced with CD80 genes and MHC II genes syngeneic to the recipient.
4175 19557412 We also demonstrate that uveal melanoma MHC II vaccines activate uveal melanoma-specific, cytolytic CD8(+) T cells that do not lyse normal fibroblasts or other tumor cells.
4176 19557412 Surprisingly, the CD8(+) T cells are cytolytic for HLA-A syngeneic and MHC I-mismatched uveal melanomas.
4177 19557412 Collectively, these studies demonstrate that MHC II uveal melanoma vaccines are potent activators of tumor-specific CD4(+) and CD8(+) T cells and suggest that the non-conventional intracellular trafficking pattern of MHC II may contribute to their enhanced immunogenicity.
4178 19557412 Since MHC I compatibility is unnecessary for the activation of cytolytic CD8(+) T cells, the vaccines could be used in uveal melanoma patients without regard to MHC I genotype.
4179 19557412 Uveal melanoma cell-based vaccines express MHC II molecules that traffic via the endocytic and secretory pathways and activate CD8+ cytotoxic, tumor-specific T cells.
4180 19557412 MHC II uveal melanoma vaccines are MHC class I(+) uveal melanoma cells transduced with CD80 genes and MHC II genes syngeneic to the recipient.
4181 19557412 We also demonstrate that uveal melanoma MHC II vaccines activate uveal melanoma-specific, cytolytic CD8(+) T cells that do not lyse normal fibroblasts or other tumor cells.
4182 19557412 Surprisingly, the CD8(+) T cells are cytolytic for HLA-A syngeneic and MHC I-mismatched uveal melanomas.
4183 19557412 Collectively, these studies demonstrate that MHC II uveal melanoma vaccines are potent activators of tumor-specific CD4(+) and CD8(+) T cells and suggest that the non-conventional intracellular trafficking pattern of MHC II may contribute to their enhanced immunogenicity.
4184 19557412 Since MHC I compatibility is unnecessary for the activation of cytolytic CD8(+) T cells, the vaccines could be used in uveal melanoma patients without regard to MHC I genotype.
4185 19557412 Uveal melanoma cell-based vaccines express MHC II molecules that traffic via the endocytic and secretory pathways and activate CD8+ cytotoxic, tumor-specific T cells.
4186 19557412 MHC II uveal melanoma vaccines are MHC class I(+) uveal melanoma cells transduced with CD80 genes and MHC II genes syngeneic to the recipient.
4187 19557412 We also demonstrate that uveal melanoma MHC II vaccines activate uveal melanoma-specific, cytolytic CD8(+) T cells that do not lyse normal fibroblasts or other tumor cells.
4188 19557412 Surprisingly, the CD8(+) T cells are cytolytic for HLA-A syngeneic and MHC I-mismatched uveal melanomas.
4189 19557412 Collectively, these studies demonstrate that MHC II uveal melanoma vaccines are potent activators of tumor-specific CD4(+) and CD8(+) T cells and suggest that the non-conventional intracellular trafficking pattern of MHC II may contribute to their enhanced immunogenicity.
4190 19557412 Since MHC I compatibility is unnecessary for the activation of cytolytic CD8(+) T cells, the vaccines could be used in uveal melanoma patients without regard to MHC I genotype.
4191 19557412 Uveal melanoma cell-based vaccines express MHC II molecules that traffic via the endocytic and secretory pathways and activate CD8+ cytotoxic, tumor-specific T cells.
4192 19557412 MHC II uveal melanoma vaccines are MHC class I(+) uveal melanoma cells transduced with CD80 genes and MHC II genes syngeneic to the recipient.
4193 19557412 We also demonstrate that uveal melanoma MHC II vaccines activate uveal melanoma-specific, cytolytic CD8(+) T cells that do not lyse normal fibroblasts or other tumor cells.
4194 19557412 Surprisingly, the CD8(+) T cells are cytolytic for HLA-A syngeneic and MHC I-mismatched uveal melanomas.
4195 19557412 Collectively, these studies demonstrate that MHC II uveal melanoma vaccines are potent activators of tumor-specific CD4(+) and CD8(+) T cells and suggest that the non-conventional intracellular trafficking pattern of MHC II may contribute to their enhanced immunogenicity.
4196 19557412 Since MHC I compatibility is unnecessary for the activation of cytolytic CD8(+) T cells, the vaccines could be used in uveal melanoma patients without regard to MHC I genotype.
4197 19557412 Uveal melanoma cell-based vaccines express MHC II molecules that traffic via the endocytic and secretory pathways and activate CD8+ cytotoxic, tumor-specific T cells.
4198 19557412 MHC II uveal melanoma vaccines are MHC class I(+) uveal melanoma cells transduced with CD80 genes and MHC II genes syngeneic to the recipient.
4199 19557412 We also demonstrate that uveal melanoma MHC II vaccines activate uveal melanoma-specific, cytolytic CD8(+) T cells that do not lyse normal fibroblasts or other tumor cells.
4200 19557412 Surprisingly, the CD8(+) T cells are cytolytic for HLA-A syngeneic and MHC I-mismatched uveal melanomas.
4201 19557412 Collectively, these studies demonstrate that MHC II uveal melanoma vaccines are potent activators of tumor-specific CD4(+) and CD8(+) T cells and suggest that the non-conventional intracellular trafficking pattern of MHC II may contribute to their enhanced immunogenicity.
4202 19557412 Since MHC I compatibility is unnecessary for the activation of cytolytic CD8(+) T cells, the vaccines could be used in uveal melanoma patients without regard to MHC I genotype.
4203 19576942 Although incubation of DCs with these EtxB-peptide conjugates as such did not induce DC maturation in vitro MHC class I antigen presentation was much more efficient as compared to peptide alone.
4204 19577301 However, there were no major changes in the expression levels of transcripts for cell surface proteins (MHC I, MHC II 2 beta-chain, TCR-beta, TLR-7, DCAR, CD44, and CD58) and cytokines (IL-2, IFN-gamma, RANTES, MIP-1beta-like and MCP-1 like chemokines).
4205 19617574 The ability of CD8(+) T cells to engage a diverse range of peptide-major histocompatibility complex (MHC) complexes can also lead to cross-recognition of self and nonself peptide-MHC complexes and thus directly contribute toward allograft rejection or autoimmunity.
4206 19617574 Functional characterization of a human leukocyte antigen (HLA) Cw*0602-restricted cytomegalovirus-specific CD8(+) T-cell response revealed an unusual dual specificity toward a pp65 epitope and the alloantigen HLA DR4.
4207 19617574 Furthermore, allostimulation of peripheral blood lymphocytes with HLA DRB*0401-expressing cells rapidly expanded CD8(+) T cells, which recognized the pp65 epitope in the context of HLA Cw*0602.
4208 19656991 Age-dependent association between low frequency of CD27/CD28 expression on pp65 CD8+ T cells and cytomegalovirus replication after transplantation.
4209 19656991 In this cross-sectional study of 42 solid organ transplant recipients, the association of human cytomegalovirus (HCMV) replication and age with the phenotype of the HCMV-specific CD8(+) T cells was analyzed by using the CMV pp65 HLA-A*0201 pentamer.
4210 19656991 A correlation between the proportion of CD28(-) HCMV-specific CD8(+) T cells and age was observed in patients without HCMV replication (r = 0.50; P = 0.02) but not in patients with HCMV replication (r = -0.05; P = 0.83), a finding which differs from that observed for total CD8(+) T cells.
4211 19656991 Within the group of patients younger than 50 years of age, patients with HCVM replication after transplantation had higher percentages of CD28(-) HCMV-specific CD8(+) T cells (85.6 compared with 58.7% for patients without HCMV replication; P = 0.004) and CD27(-) HCMV-specific CD8(+) T cells (90.7 compared with 68.8% for patients without HCMV replication; P = 0.03).
4212 19656991 However, in patients older than age 50 years, a high frequency of these two subpopulations was observed in patients both with and without previous HCMV replication (for CD28(-) HCMV-specific CD8(+) T cells, 84.4 and 80.9%, respectively [P = 0.39]; for CD27(-) HCMV-specific CD8(+) T cells 86.6 and 81.5%, respectively [P = 0.16]).
4213 19656991 In conclusion, the present study shows that in the group of recipients younger than age 50 years, HCMV replication after transplantation is associated with a high percentage of CD27(-) and CD28(-) HCMV-specific CD8(+) T cells.
4214 19656991 These results suggest that the increased percentage of CD27(-) or CD28(-) HCMV-specific subsets can be considered a biomarker of HCMV replication in solid organ transplant recipients younger than age 50 years but not in older patients.
4215 19667042 In this report we show that MHC-II-restricted Chlamydia-specific CD4 T-cell clones recognize infected upper reproductive tract epithelial cells as early as 12 h postinfection.
4216 19667042 Beta IFN (IFN-beta) and IFN-gamma have different effects on T-cell activation, with IFN-beta blunting IFN-gamma-induced upregulation of epithelial cell surface MHC-II and T-cell activation.
4217 19667042 Individual CD4 T-cell clones differed in their degrees of dependence on IFN-gamma-regulated MHC-II for controlling Chlamydia replication in epithelial cells in vitro.
4218 19667042 We discuss our data as they relate to published studies with IFN knockout mice, proposing a straightforward interpretation of the existing literature based on CD4 T-cell interactions with the infected reproductive tract epithelium.
4219 19669608 These cells were cultured with cytokines GM-CSF, IL-4, and TNFalpha to induce their maturation.
4220 19669608 Phenotypically, FACS analysis showed that they expressed high levels of MHC II, CD11b, CD80, and CD86 antigen, and were negative for CD8alpha.
4221 19689295 In the second part of this review, we summarize the importance of CD4+ T cell help in peptide-based vaccine strategies and offer a potential strategy to improve peptide-based vaccines through the generation of both HLA class I and class II vaccine specific-immune responses.
4222 19689293 They recognize lipid antigens rather than peptides, and respond to these when presented by a non-classical class I MHC molecule, CD1d.
4223 19689476 These three peptides induced HLA-A26-restricted cytotoxic T lymphocytes from HLA-A*2601-, -A*2602-, or -A*2603-positive prostate cancer patients against HLA-A*2601- and HLA-A*2603-positive cancer cells in CD8-dependent and peptide-specific manners.
4224 19728337 In vitro stimulation with human leukocyte antigen (HLA)-A*2402 (A24)-restricted peptides, RFENLGPQL (SOX6(504)) and PYYEEQARL (SOX6(628)) or the HLA-A*0201 (A2)-restricted peptide, ALFGDQDTV (SOX6(447)) was capable of inducing SOX6 peptide-specific CTLs in peripheral blood mononuclear cells derived from healthy donors and glioma patients.
4225 19728337 Furthermore, peptide vaccines of SOX6(628), which was conserved in the murine SOX6 protein and expected to bind to major histocompatibility complex (MHC) H-2(d), induced CTLs specific for SOX6(628) in H-2(d) mice.
4226 19728337 In vitro stimulation with human leukocyte antigen (HLA)-A*2402 (A24)-restricted peptides, RFENLGPQL (SOX6(504)) and PYYEEQARL (SOX6(628)) or the HLA-A*0201 (A2)-restricted peptide, ALFGDQDTV (SOX6(447)) was capable of inducing SOX6 peptide-specific CTLs in peripheral blood mononuclear cells derived from healthy donors and glioma patients.
4227 19728337 Furthermore, peptide vaccines of SOX6(628), which was conserved in the murine SOX6 protein and expected to bind to major histocompatibility complex (MHC) H-2(d), induced CTLs specific for SOX6(628) in H-2(d) mice.
4228 19739073 Treatment of tumor-bearing mice with beta-GalCer(C12) 3-14 days after tumor cell transplantation significantly inhibited the growth of the major histocompatibility complex (MHC) Class I-positive (TC-1), as well as MHC Class I-deficient (TC-1/A9) HPV16-associated tumors.
4229 19758325 Towards this end, a cationic tat-sequence was fused with an antigenic, major histocompatibility complex (MHC) class I-binding melanoma epitope (Melan-A/Mart-1 sequence: ELAGIGILTV) and then mixed with negatively charged poly(I:C) dsRNA to form peptide/nucleic acid complexes.
4230 19759892 A novel liposome-based adjuvant CAF01 for induction of CD8(+) cytotoxic T-lymphocytes (CTL) to HIV-1 minimal CTL peptides in HLA-A*0201 transgenic mice.
4231 19786555 In this study, we compared the TCR primary structures of 1489 HLA-A*0201/Melan-A(26-35)-specific CD8 T cells derived from both cohorts of patients.
4232 19830730 In the current study, we profiled the early activation of CD8+ T cells by MHC class I-restricted peptide immunization to better understand the biology of this response.
4233 19830730 Interestingly, CpG treatment modulated T-cell expression of the surface receptors PD-1 and CD25, providing insight into its possible adjuvant mechanism.
4234 19830741 HIV gag protein is efficiently cross-presented when targeted with an antibody towards the DEC-205 receptor in Flt3 ligand-mobilized murine DC.
4235 19830741 DC present exogenous proteins to MHC class I-restricted CD8+ T cells.
4236 19830741 In mice, the CD8+ or DEC-205+ DC are specialized for cross-presentation, and this subset can be increased 10-fold in numbers following Fms-like tyrosine kinase 3 ligand (Flt3L) treatment in vivo.
4237 19830741 DC cross-present HIV gag to primed CD8+ T cells, but when the antigen is delivered within an antibody to DEC-205 receptor, cross-presentation becomes 100-fold more efficient than non-targeted antigen.
4238 19837091 Each vaccine batch was analyzed for the expression of the surface maturation and differentiation molecules CD14, CD1a, CD83, CD86, MHC class II and CCR7, and the optimal expression pattern is considered as CD14(low), CD1a, CD83(high), CD86(high), MHC class II(high) and CCR7(high).
4239 19845536 Immune hierarchy among HIV-1 CD8+ T cell epitopes delivered by dendritic cells depends on MHC-I binding irrespective of mode of loading and immunization in HLA-A*0201 mice.
4240 19845536 Data from this study showed that the T-cell response, as measured by cytolytic activity and gamma-interferon (IFN-gamma)-producing CD8(+) T cells, mainly focused on two of seven administered epitopes.
4241 19846882 Induction of cross-priming of naive CD8+ T lymphocytes by recombinant bacillus Calmette-Guerin that secretes heat shock protein 70-major membrane protein-II fusion protein.
4242 19846882 Because Mycobacterium bovis bacillus Calmette-Guérin (BCG) unconvincingly activates human naive CD8(+) T cells, a rBCG (BCG-70M) that secretes a fusion protein comprising BCG-derived heat shock protein (HSP)70 and Mycobacterium leprae-derived major membrane protein (MMP)-II, one of the immunodominant Ags of M. leprae, was newly constructed to potentiate the ability of activating naive CD8(+) T cells through dendritic cells (DC).
4243 19846882 BCG-70M secreted HSP70-MMP-II fusion protein in vitro, which stimulated DC to produce IL-12p70 through TLR2.
4244 19846882 BCG-70M-infected DC activated not only memory and naive CD8(+) T cells, but also CD4(+) T cells of both types to produce IFN-gamma.
4245 19846882 The activation of these naive T cells by BCG-70M was dependent on the MHC and CD86 molecules on BCG-70M-infected DC, and was significantly inhibited by pretreatment of DC with chloroquine.
4246 19846882 When naive CD8(+) T cells were stimulated by BCG-70M-infected DC in the presence of naive CD4(+) T cells, CD62L(low)CD8(+) T cells and perforin-producing CD8(+) T cells were efficiently produced.
4247 19846882 MMP-II-reactive CD4(+) and CD8(+) memory T cells were efficiently produced in C57BL/6 mice by infection with BCG-70M.
4248 19846882 These results indicate that BCG-70M activated DC, CD4(+) T cells, and CD8(+) T cells, and the combination of HSP70 and MMP-II may be useful for inducing better T cell activation.
4249 19853910 The effect of R1, R2 and R3 on the expression of the pro- and anti-inflammatory cytokines (TNF-alpha, IL-6, and IL-12) and the co-stimulatory molecules (CD40, CD80, CD86, and MHC class II) in MDDCs was examined.
4250 19853910 The exposure of R1 caused a dose-dependent increase in the expression of TNF-alpha, IL-12, CD86 and CD40, while R2 and R3 did not up-regulate these cytokines and co-stimulatory molecules.
4251 19853910 Furthermore, we found that R1 significantly increased the NF-kappaB expression in the nucleus (in a dose-dependent manner) and promoted the degradation of total IkappaBalpha levels, indicating that the NF-kappaB signaling pathway might involve in an R1-induced DC activation.
4252 19863514 Intradermal injections of polyarginine-containing immunogenic antigens preferentially elicit Tc1 and Th1 activation and antitumour immunity.
4253 19863514 Background We previously have shown that nona-arginine protein transduction domain (R9-PTD) induced efficient protein-antigen (Ag) transduction of dendritic cells (DCs) in vitro, resulting in the efficient induction of strong Ag-specific immune responses mediated by CD8+ and CD4+ T cells and in superior antitumour effects in vivo in cancer-bearing mice.
4254 19863514 The i.d. injections of rR9-OVA also induced inflammatory cell infiltrates containing neutrophils, monocytes and lymphocytes, as well as production of inflammatory cytokines such as interferon (IFN)-gamma, interleukin-2 and IFN-inducible protein 10, with presenting SIINFEKL epitopes on major histocompatibility complex (MHC) class I molecules at the injection area. i.t. injections of rR9-OVA into EG.7 tumour mass significantly suppressed tumour growth, and these effects were completely abrogated by the depletion of CD8+ T cells.
4255 19882243 Herein, to provide information for construction of efficient HCV polytope vaccine candidates, one H-2D(d) (E2(405-414):E(2)) and two HLA-A*0201 (E1(363-372):E(1) and Core(35-44):C)-restricted CD8(+) T-cell epitopes of HCV were selected.
4256 19893892 One of the main strategies to target DNA-encoded antigens to the MHC II compartment is expressing the antigen within the Lysosome-Associated Membrane Protein (LAMP).
4257 19901990 Furthermore, H5(246-260) epitope was found to be presented by both major histocompatibility complex (MHC) class I and II molecules, leading to activation of CD4+ and CD8+ T cell subsets, marked by proliferation and expression of interferon (IFN)-gamma by both of these cell subsets as well as the expression of granzyme A by CD8+ T cells.
4258 19904532 We describe herein a novel HLA-A*0201-restricted epitope, encompassing amino acids 828-836 (residues QIAKGMSYL), which is naturally presented by various HER-2/neu (+) tumor cell lines.
4259 19904532 HER-2/neu(828-836), [HER-2(9(828))], possesses two anchor residues and stabilized HLA-A*0201 on T2 cells in a concentration-dependent Class I binding assay.
4260 19904532 HER-2(9(828)) was found to be immunogenic in HLA-A*0201 transgenic (HHD) mice inducing peptide-specific and functionally potent CTL and long-lasting anti-tumor immunity.
4261 19904532 Most important, using HLA-A*0201 pentamer analysis we could detect increased ex vivo frequencies of CD8(+) T-lymphocytes specifically recognizing HER-2(9(828)) in 8 out of 20 HLA-A*0201(+) HER-2/neu (+) breast cancer patients.
4262 19904532 Moreover, HER-2(9(828))-specific human CTL recognized the tumor cell line SKOV3.A2 as well as the primary RS.A2.1.DR1 tumor cell line both expressing HER-2/neu and HLA-A*0201.
4263 19904532 Finally, therapeutic vaccination with HER-2(9(828)) in HHD mice was proven effective against established transplantable ALC.A2.1.HER tumors, inducing complete tumor regression in 50% of mice.
4264 19904532 We describe herein a novel HLA-A*0201-restricted epitope, encompassing amino acids 828-836 (residues QIAKGMSYL), which is naturally presented by various HER-2/neu (+) tumor cell lines.
4265 19904532 HER-2/neu(828-836), [HER-2(9(828))], possesses two anchor residues and stabilized HLA-A*0201 on T2 cells in a concentration-dependent Class I binding assay.
4266 19904532 HER-2(9(828)) was found to be immunogenic in HLA-A*0201 transgenic (HHD) mice inducing peptide-specific and functionally potent CTL and long-lasting anti-tumor immunity.
4267 19904532 Most important, using HLA-A*0201 pentamer analysis we could detect increased ex vivo frequencies of CD8(+) T-lymphocytes specifically recognizing HER-2(9(828)) in 8 out of 20 HLA-A*0201(+) HER-2/neu (+) breast cancer patients.
4268 19904532 Moreover, HER-2(9(828))-specific human CTL recognized the tumor cell line SKOV3.A2 as well as the primary RS.A2.1.DR1 tumor cell line both expressing HER-2/neu and HLA-A*0201.
4269 19904532 Finally, therapeutic vaccination with HER-2(9(828)) in HHD mice was proven effective against established transplantable ALC.A2.1.HER tumors, inducing complete tumor regression in 50% of mice.
4270 19904532 We describe herein a novel HLA-A*0201-restricted epitope, encompassing amino acids 828-836 (residues QIAKGMSYL), which is naturally presented by various HER-2/neu (+) tumor cell lines.
4271 19904532 HER-2/neu(828-836), [HER-2(9(828))], possesses two anchor residues and stabilized HLA-A*0201 on T2 cells in a concentration-dependent Class I binding assay.
4272 19904532 HER-2(9(828)) was found to be immunogenic in HLA-A*0201 transgenic (HHD) mice inducing peptide-specific and functionally potent CTL and long-lasting anti-tumor immunity.
4273 19904532 Most important, using HLA-A*0201 pentamer analysis we could detect increased ex vivo frequencies of CD8(+) T-lymphocytes specifically recognizing HER-2(9(828)) in 8 out of 20 HLA-A*0201(+) HER-2/neu (+) breast cancer patients.
4274 19904532 Moreover, HER-2(9(828))-specific human CTL recognized the tumor cell line SKOV3.A2 as well as the primary RS.A2.1.DR1 tumor cell line both expressing HER-2/neu and HLA-A*0201.
4275 19904532 Finally, therapeutic vaccination with HER-2(9(828)) in HHD mice was proven effective against established transplantable ALC.A2.1.HER tumors, inducing complete tumor regression in 50% of mice.
4276 19904532 We describe herein a novel HLA-A*0201-restricted epitope, encompassing amino acids 828-836 (residues QIAKGMSYL), which is naturally presented by various HER-2/neu (+) tumor cell lines.
4277 19904532 HER-2/neu(828-836), [HER-2(9(828))], possesses two anchor residues and stabilized HLA-A*0201 on T2 cells in a concentration-dependent Class I binding assay.
4278 19904532 HER-2(9(828)) was found to be immunogenic in HLA-A*0201 transgenic (HHD) mice inducing peptide-specific and functionally potent CTL and long-lasting anti-tumor immunity.
4279 19904532 Most important, using HLA-A*0201 pentamer analysis we could detect increased ex vivo frequencies of CD8(+) T-lymphocytes specifically recognizing HER-2(9(828)) in 8 out of 20 HLA-A*0201(+) HER-2/neu (+) breast cancer patients.
4280 19904532 Moreover, HER-2(9(828))-specific human CTL recognized the tumor cell line SKOV3.A2 as well as the primary RS.A2.1.DR1 tumor cell line both expressing HER-2/neu and HLA-A*0201.
4281 19904532 Finally, therapeutic vaccination with HER-2(9(828)) in HHD mice was proven effective against established transplantable ALC.A2.1.HER tumors, inducing complete tumor regression in 50% of mice.
4282 19904532 We describe herein a novel HLA-A*0201-restricted epitope, encompassing amino acids 828-836 (residues QIAKGMSYL), which is naturally presented by various HER-2/neu (+) tumor cell lines.
4283 19904532 HER-2/neu(828-836), [HER-2(9(828))], possesses two anchor residues and stabilized HLA-A*0201 on T2 cells in a concentration-dependent Class I binding assay.
4284 19904532 HER-2(9(828)) was found to be immunogenic in HLA-A*0201 transgenic (HHD) mice inducing peptide-specific and functionally potent CTL and long-lasting anti-tumor immunity.
4285 19904532 Most important, using HLA-A*0201 pentamer analysis we could detect increased ex vivo frequencies of CD8(+) T-lymphocytes specifically recognizing HER-2(9(828)) in 8 out of 20 HLA-A*0201(+) HER-2/neu (+) breast cancer patients.
4286 19904532 Moreover, HER-2(9(828))-specific human CTL recognized the tumor cell line SKOV3.A2 as well as the primary RS.A2.1.DR1 tumor cell line both expressing HER-2/neu and HLA-A*0201.
4287 19904532 Finally, therapeutic vaccination with HER-2(9(828)) in HHD mice was proven effective against established transplantable ALC.A2.1.HER tumors, inducing complete tumor regression in 50% of mice.
4288 19913062 Ovalbumin (OVA) MHC class I epitope peptide (OVA(257-264): SIINFEKL) was selected as a model antigen and polyhistidine was used to facilitate the cytosolic delivery of the antigen-Hsp70 after endocytic uptake.
4289 19917498 Unlike Vaccinia virus, cowpox virus prevents stimulation of CD8(+) T cells, a block that correlated with retention of MHC class I in the endoplasmic reticulum by the cowpox virus protein CPXV203.
4290 19917498 Here, we demonstrate the contribution of an additional viral protein, CPXV12, which interferes with MHC class I/peptide complex formation by inhibiting peptide translocation by the transporter associated with antigen processing (TAP).
4291 19917498 Unlike Vaccinia virus, cowpox virus prevents stimulation of CD8(+) T cells, a block that correlated with retention of MHC class I in the endoplasmic reticulum by the cowpox virus protein CPXV203.
4292 19917498 Here, we demonstrate the contribution of an additional viral protein, CPXV12, which interferes with MHC class I/peptide complex formation by inhibiting peptide translocation by the transporter associated with antigen processing (TAP).
4293 19923463 This approach, extensively used for MHC class I-restricted T cells, has met very limited success with class II peptide-MHC complex tetramers (pMHCT-2) for the detection of CD4(+)-specific T cells.
4294 19930045 Both CD4(+) and CD8(+) T cells are important in protection against Mycobacterium tuberculosis infection.
4295 19930045 The CD8(+) T cells were detected by staining lymphocytes with pentameric major histocompatibility complex (MHC) class I H-2D(b-)Mtb32a(209-318) peptide complex and were analysed by flow cytometry.
4296 19930045 The pulmonary CD8(+) T cells from the BCG-vaccinated M. tuberculosis-infected mice produced interferon-gamma in response to Mtb32a(209-318) peptide on day 7 of the infection, whereas those of unvaccinated mice did not.
4297 19940864 We found that the co-administration of a DNA vaccine in conjunction with a DNA encoding a xenogenic major histocompatibility complex (MHC) molecule could significantly enhance the E7-specific CD8+ T-cell immune responses and antitumor effects against an E7-expressing tumor, TC-1, in C57BL/6 tumor-bearing mice.
4298 19952953 Novel immunogenic HLA-A*0201-restricted epidermal growth factor receptor-specific T-cell epitope in head and neck cancer patients.
4299 19952953 To permit combinatorial EGFR-targeted immunotherapy, we identified a novel immunogenic wild-type sequence peptide, EGFR853-861 and modified its anchor sequence to enhance HLA-A*0201 binding and stimulation of cross-reactive anti-wild-type EGFR853-861-specific CTL.
4300 19952953 Novel immunogenic HLA-A*0201-restricted epidermal growth factor receptor-specific T-cell epitope in head and neck cancer patients.
4301 19952953 To permit combinatorial EGFR-targeted immunotherapy, we identified a novel immunogenic wild-type sequence peptide, EGFR853-861 and modified its anchor sequence to enhance HLA-A*0201 binding and stimulation of cross-reactive anti-wild-type EGFR853-861-specific CTL.
4302 20002212 Extensive major histocompatibility complex class I binding promiscuity for Mycobacterium tuberculosis TB10.4 peptides and immune dominance of human leucocyte antigen (HLA)-B*0702 and HLA-B*0801 alleles in TB10.4 CD8 T-cell responses.
4303 20002212 The molecular definition of major histocompatibility complex (MHC) class I-presented CD8(+) T-cell epitopes from clinically relevant Mycobacterium tuberculosis (Mtb) target proteins will aid in the rational design of T-cell-based diagnostics of tuberculosis (TB) and the measurement of TB vaccine-take.
4304 20002212 Affinity (50% effective dose) and off-rate (half life) analysis of candidate Mtb peptides will help to define the conditions for CD8(+) T-cell interaction with their nominal MHC class I-peptide ligands.
4305 20002212 HLA-B alleles served as the dominant MHC class I restricting molecules for anti-Mtb TB10.4-specific CD8(+) T-cell responses measured in CD8(+) T cells from patients with pulmonary TB.
4306 20002212 Extensive major histocompatibility complex class I binding promiscuity for Mycobacterium tuberculosis TB10.4 peptides and immune dominance of human leucocyte antigen (HLA)-B*0702 and HLA-B*0801 alleles in TB10.4 CD8 T-cell responses.
4307 20002212 The molecular definition of major histocompatibility complex (MHC) class I-presented CD8(+) T-cell epitopes from clinically relevant Mycobacterium tuberculosis (Mtb) target proteins will aid in the rational design of T-cell-based diagnostics of tuberculosis (TB) and the measurement of TB vaccine-take.
4308 20002212 Affinity (50% effective dose) and off-rate (half life) analysis of candidate Mtb peptides will help to define the conditions for CD8(+) T-cell interaction with their nominal MHC class I-peptide ligands.
4309 20002212 HLA-B alleles served as the dominant MHC class I restricting molecules for anti-Mtb TB10.4-specific CD8(+) T-cell responses measured in CD8(+) T cells from patients with pulmonary TB.
4310 20002212 Extensive major histocompatibility complex class I binding promiscuity for Mycobacterium tuberculosis TB10.4 peptides and immune dominance of human leucocyte antigen (HLA)-B*0702 and HLA-B*0801 alleles in TB10.4 CD8 T-cell responses.
4311 20002212 The molecular definition of major histocompatibility complex (MHC) class I-presented CD8(+) T-cell epitopes from clinically relevant Mycobacterium tuberculosis (Mtb) target proteins will aid in the rational design of T-cell-based diagnostics of tuberculosis (TB) and the measurement of TB vaccine-take.
4312 20002212 Affinity (50% effective dose) and off-rate (half life) analysis of candidate Mtb peptides will help to define the conditions for CD8(+) T-cell interaction with their nominal MHC class I-peptide ligands.
4313 20002212 HLA-B alleles served as the dominant MHC class I restricting molecules for anti-Mtb TB10.4-specific CD8(+) T-cell responses measured in CD8(+) T cells from patients with pulmonary TB.
4314 20010627 FC-CD40L showed an enhanced expression of CD80, CD86, CD54 and MHC class II molecules and elicited a strong in vitro immune response in a syngeneic mixed lymphocyte reaction.
4315 20010627 Splenocytes from mice treated with FC-CD40L had a dramatic increase in the production of IL-17, IL-6 and IFN-gamma, compared with controls.
4316 20011145 Here, we report the results from the computational characterization of MSP1, precursor (1720 residue) and screening of highest scoring potential CTL epitopes for 1712 overlapping peptides binding to thirty four HLA class-I alleles and twelve HLA class-I supertypes (5 HLA-A and 7 HLA-B) using bioinformatics tools.
4317 20033649 Ly49 receptors in rodents, like KIR in humans, play an integral role in the regulation of NK cell activity.
4318 20033649 Additionally, we describe a method for the mutagenesis of Ly49 and MHC ligands that can be used to define the motifs conferring receptor specificity for their ligands.
4319 20033649 Further elucidation of Ly49 ligands is required to continue to define the role of Ly49 in regulating NK cell effector function and may give vital clues to the role of KIR in human health and disease.
4320 20060099 Liposomal conjugates with peptide M1 58-66, an HLA-A*0201-binding CTL epitope present within the amino-acid sequence of the M1 coding region, successfully induced antigen-specific CD8(+) T-cells and CTLs in HLA-A*0201-transgenic mice.
4321 20067538 Vaccinia virus decreases major histocompatibility complex (MHC) class II antigen presentation, T-cell priming, and peptide association with MHC class II.
4322 20067538 VACV significantly decreased nitric oxide production by peritoneal exudate cells and the RAW macrophage cell line in response to lipopolysaccharide (LPS) and interferon (IFN)-gamma, decreased class II MHC expression on APCs, and induced apoptosis in macrophages and dendritic cells.
4323 20067538 Vaccinia virus decreases major histocompatibility complex (MHC) class II antigen presentation, T-cell priming, and peptide association with MHC class II.
4324 20067538 VACV significantly decreased nitric oxide production by peritoneal exudate cells and the RAW macrophage cell line in response to lipopolysaccharide (LPS) and interferon (IFN)-gamma, decreased class II MHC expression on APCs, and induced apoptosis in macrophages and dendritic cells.
4325 20091859 CIITA-driven MHC-II positive tumor cells: preventive vaccines and superior generators of antitumor CD4+ T lymphocytes for immunotherapy.
4326 20091859 In our study, we have investigated whether tumors of distinct histological origin can be rejected if expressing CIITA-driven MHC class II molecules.
4327 20091859 Adoptive cell transfer experiments demonstrated that tumor immunity correlates with the efficient priming of CD4(+) T helper cells and the consequent activation of CD8(+) T lymphocytes.
4328 20091859 Importantly, CD4(+) T cells were clearly superior to CD8(+) T cells in antitumor protective function.
4329 20116862 The activation markers included major histocompatibility complex class II (MHC II), intracellular interferon gamma (IFN-gamma) and interleukin 4 (IL-4).
4330 20116862 Following EHV-1 stimulation, the MHC II expression index (EI) increased significantly in CD2+CD4+CD8- and CD2+CD4-CD8+ subsets of the infected group.
4331 20116862 At 4 days after incubation, the non-antigen stimulated CD2+CD4-CD8- subset of the infected group expressed a high percentage (61.1%) of MHC II.
4332 20116862 The IFN-gamma EI was significantly higher in infected foals in all major T cell subsets (CD2+) while only the CD2+CD4+CD8- subset showed a significant increase in intracellular IL-4 EI.
4333 20116862 The high MHC II expression in the CD2+CD4-CD8- subset suggests that this T cell subset may represent a gammadelta TCR repertoire and thereby plays an important role as antigen presenting cells in the horse, as reported in other species.
4334 20116862 The activation markers included major histocompatibility complex class II (MHC II), intracellular interferon gamma (IFN-gamma) and interleukin 4 (IL-4).
4335 20116862 Following EHV-1 stimulation, the MHC II expression index (EI) increased significantly in CD2+CD4+CD8- and CD2+CD4-CD8+ subsets of the infected group.
4336 20116862 At 4 days after incubation, the non-antigen stimulated CD2+CD4-CD8- subset of the infected group expressed a high percentage (61.1%) of MHC II.
4337 20116862 The IFN-gamma EI was significantly higher in infected foals in all major T cell subsets (CD2+) while only the CD2+CD4+CD8- subset showed a significant increase in intracellular IL-4 EI.
4338 20116862 The high MHC II expression in the CD2+CD4-CD8- subset suggests that this T cell subset may represent a gammadelta TCR repertoire and thereby plays an important role as antigen presenting cells in the horse, as reported in other species.
4339 20116862 The activation markers included major histocompatibility complex class II (MHC II), intracellular interferon gamma (IFN-gamma) and interleukin 4 (IL-4).
4340 20116862 Following EHV-1 stimulation, the MHC II expression index (EI) increased significantly in CD2+CD4+CD8- and CD2+CD4-CD8+ subsets of the infected group.
4341 20116862 At 4 days after incubation, the non-antigen stimulated CD2+CD4-CD8- subset of the infected group expressed a high percentage (61.1%) of MHC II.
4342 20116862 The IFN-gamma EI was significantly higher in infected foals in all major T cell subsets (CD2+) while only the CD2+CD4+CD8- subset showed a significant increase in intracellular IL-4 EI.
4343 20116862 The high MHC II expression in the CD2+CD4-CD8- subset suggests that this T cell subset may represent a gammadelta TCR repertoire and thereby plays an important role as antigen presenting cells in the horse, as reported in other species.
4344 20116862 The activation markers included major histocompatibility complex class II (MHC II), intracellular interferon gamma (IFN-gamma) and interleukin 4 (IL-4).
4345 20116862 Following EHV-1 stimulation, the MHC II expression index (EI) increased significantly in CD2+CD4+CD8- and CD2+CD4-CD8+ subsets of the infected group.
4346 20116862 At 4 days after incubation, the non-antigen stimulated CD2+CD4-CD8- subset of the infected group expressed a high percentage (61.1%) of MHC II.
4347 20116862 The IFN-gamma EI was significantly higher in infected foals in all major T cell subsets (CD2+) while only the CD2+CD4+CD8- subset showed a significant increase in intracellular IL-4 EI.
4348 20116862 The high MHC II expression in the CD2+CD4-CD8- subset suggests that this T cell subset may represent a gammadelta TCR repertoire and thereby plays an important role as antigen presenting cells in the horse, as reported in other species.
4349 20124097 A novel HLA (HLA-A*0201) transgenic rabbit model for preclinical evaluation of human CD8+ T cell epitope-based vaccines against ocular herpes.
4350 20124097 We introduced a novel humanized HLA-A*0201 transgenic (HLA Tg) rabbit model to assess the protective efficacy of a human CD8(+) T cell epitope-based vaccine against primary ocular herpes infection and disease.
4351 20124097 Each of the three immunodominant human CD8(+) T cell peptide epitopes from HSV-1 glycoprotein D (gD(53-61), gD(70-78), and gD(278-286)) were joined with a promiscuous human CD4(+) T cell peptide epitope (gD(49-82)) to construct three separate pairs of CD4-CD8 peptides.
4352 20124097 Immunization induced HSV-gD(49-82)-specific CD4(+) T cells in draining lymph node (DLN); induced HLA-restricted HSV-gD(53-61), gD(70-78), and gD(278-286)-specific CD8(+) T cells in DLN, conjunctiva, and trigeminal ganglia and reduced HSV-1 replication in tears and corneal eye disease after ocular HSV-1 challenge.
4353 20124097 A novel HLA (HLA-A*0201) transgenic rabbit model for preclinical evaluation of human CD8+ T cell epitope-based vaccines against ocular herpes.
4354 20124097 We introduced a novel humanized HLA-A*0201 transgenic (HLA Tg) rabbit model to assess the protective efficacy of a human CD8(+) T cell epitope-based vaccine against primary ocular herpes infection and disease.
4355 20124097 Each of the three immunodominant human CD8(+) T cell peptide epitopes from HSV-1 glycoprotein D (gD(53-61), gD(70-78), and gD(278-286)) were joined with a promiscuous human CD4(+) T cell peptide epitope (gD(49-82)) to construct three separate pairs of CD4-CD8 peptides.
4356 20124097 Immunization induced HSV-gD(49-82)-specific CD4(+) T cells in draining lymph node (DLN); induced HLA-restricted HSV-gD(53-61), gD(70-78), and gD(278-286)-specific CD8(+) T cells in DLN, conjunctiva, and trigeminal ganglia and reduced HSV-1 replication in tears and corneal eye disease after ocular HSV-1 challenge.
4357 20136618 MHC class I-restricted CD8 cytotoxic T lymphocytes (CTL) are essential for protective immunity to Tuberculosis.
4358 20155490 Potential epitopes can be identified with major histocompatibility complex (MHC)-binding algorithms, and the ability to bind to MHC class I or class II indicates a predominantly CD4(+) or CD8(+) T cell response.
4359 20156444 We report that high concentrations of up to 10% of DMSO for 1 hour do not affect the cell viability, the magnitude or the functional profile of CD4(+) and CD8(+) T cell responses, regardless of antigen specificity and HLA class I restriction.
4360 20156506 Our hypothesis is that influenza-derived HLA-class I-restricted epitopes can be identified for use as a reagent to monitor and quantitate human CD8(+) T-cell responses and for vaccine development to induce protective cellular immunity.
4361 20158470 The cytoplasmic location of L. monocytogenes is significant as this potentiates entry of antigens into the MHC Class I antigen processing pathway leading to priming of specific CD8(+) T cell responses.
4362 20176741 Day 3 ROS(lo) DCs were highly responsive to TLR stimuli such as LPS and zymosan by rapid upregulation of CD80, CD86, and MHC class II, in contrast to the low response of day 6 ROS(hi) DCs.
4363 20176741 ROS(hi) DCs could not initiate and sustain a significant level of NF-kappaB phosphorylation in response to LPS and zymosan, although demonstrating hyperactivation of p38 MAPK by LPS, in a fashion disparate to ROS(lo) DCs.
4364 20178101 We have recently proposed that the progression or regression of a tumor lesion in cancer patients undergoing immunotherapy could be predetermined by the molecular mechanism responsible for the MHC Class I alteration and not by the type of immunotherapy used, i.e., interleukin-2 (IL-2), Bacillus Calmette-Guèrin (BCG), interferon-alpha (IFN-alpha), peptides alone, dendritic cells loaded with peptides, protein-bound polysaccharide etc.
4365 20182872 Further study demonstrated that the HLA-A*0201-restricted Cytotoxic T lymphocytes (CTL) epitopes Hpa525 (PAFSYSFFV), Hpa277 (KMLKSFLKA) and Hpa405 (WLSLLFKKL) from human heparanase could induce a potent anti-tumor immune response in vitro.
4366 20182872 Our results demonstrated that the effectors from heparanase peptide-immunized mice could effectively lyse various tumor cells that were heparanase positive and HLA-A*0201 matched.
4367 20182872 These results suggest that Hpa525, Hpa277, and Hpa405 peptides are novel HLA-A*0201-restricted CTL epitopes capable of inducing heparanase-specific CTLs in mice.
4368 20182872 Further study demonstrated that the HLA-A*0201-restricted Cytotoxic T lymphocytes (CTL) epitopes Hpa525 (PAFSYSFFV), Hpa277 (KMLKSFLKA) and Hpa405 (WLSLLFKKL) from human heparanase could induce a potent anti-tumor immune response in vitro.
4369 20182872 Our results demonstrated that the effectors from heparanase peptide-immunized mice could effectively lyse various tumor cells that were heparanase positive and HLA-A*0201 matched.
4370 20182872 These results suggest that Hpa525, Hpa277, and Hpa405 peptides are novel HLA-A*0201-restricted CTL epitopes capable of inducing heparanase-specific CTLs in mice.
4371 20182872 Further study demonstrated that the HLA-A*0201-restricted Cytotoxic T lymphocytes (CTL) epitopes Hpa525 (PAFSYSFFV), Hpa277 (KMLKSFLKA) and Hpa405 (WLSLLFKKL) from human heparanase could induce a potent anti-tumor immune response in vitro.
4372 20182872 Our results demonstrated that the effectors from heparanase peptide-immunized mice could effectively lyse various tumor cells that were heparanase positive and HLA-A*0201 matched.
4373 20182872 These results suggest that Hpa525, Hpa277, and Hpa405 peptides are novel HLA-A*0201-restricted CTL epitopes capable of inducing heparanase-specific CTLs in mice.
4374 20300588 Tomatine adjuvantation of protective immunity to a major pre-erythrocytic vaccine candidate of malaria is mediated via CD8+ T cell release of IFN-gamma.
4375 20300588 Using a defined MHC-class-I-restricted CS epitope in a Plasmodium berghei rodent model, antigen-specific cytotoxic T lymphocyte activity and IFN-gamma secretion ex vivo were both significantly enhanced compared to responses detected from similarly stimulated splenocytes from naive and tomatine-saline-immunized mice.
4376 20300588 Further, through lymphocyte depletion it is demonstrated that antigen-specific IFN-gamma is produced exclusively by the CD8(+) T cell subset.
4377 20300588 We conclude that the processing of the P. berghei CS peptide as an exogenous antigen and its presentation via MHC class I molecules to CD8(+) T cells leads to an immune response that is an in vitro correlate of protection against pre-erythrocytic malaria.
4378 20300588 Tomatine adjuvantation of protective immunity to a major pre-erythrocytic vaccine candidate of malaria is mediated via CD8+ T cell release of IFN-gamma.
4379 20300588 Using a defined MHC-class-I-restricted CS epitope in a Plasmodium berghei rodent model, antigen-specific cytotoxic T lymphocyte activity and IFN-gamma secretion ex vivo were both significantly enhanced compared to responses detected from similarly stimulated splenocytes from naive and tomatine-saline-immunized mice.
4380 20300588 Further, through lymphocyte depletion it is demonstrated that antigen-specific IFN-gamma is produced exclusively by the CD8(+) T cell subset.
4381 20300588 We conclude that the processing of the P. berghei CS peptide as an exogenous antigen and its presentation via MHC class I molecules to CD8(+) T cells leads to an immune response that is an in vitro correlate of protection against pre-erythrocytic malaria.
4382 20363973 Sequences covering predicted and tested HLA class I-restricted epitopes (peptides) within the HIV-Gag, Pol, and Nef regions were obtained from 26 study subjects resulting in 1492 patient-specific peptide pairs.
4383 20373997 Analyses of the specificity of CD4 T cells during the primary immune response to influenza virus reveals dramatic MHC-linked asymmetries in reactivity to individual viral proteins.
4384 20373997 CD4 T cells play an important role in the immune response to this pathogen through the secretion of antiviral cytokines, and by providing help to CD8 T cells and B cells to promote the development of immunological memory and neutralizing antibody responses.
4385 20373997 In the study reported here, overlapping peptides representing 5 different influenza viral proteins were used in EliSpot assays to enumerate and identify the specificity of anti-influenza CD4 T cells directly ex vivo following infection of mice with influenza virus, using two strains that express unrelated MHC class II molecules.
4386 20373997 These experiments evaluated whether the reactivity of CD4 T cells generally tracked with particular influenza proteins, or whether MHC preferences were the predominant factor dictating anti-CD4 T-cell specificity in the primary immune response.
4387 20373997 Given the diversity of human MHC class II molecules, these findings have important implications for the ability to rationally design a vaccine that will generate a specific CD4 T-cell immune response that is effective across diverse human populations.
4388 20373997 Analyses of the specificity of CD4 T cells during the primary immune response to influenza virus reveals dramatic MHC-linked asymmetries in reactivity to individual viral proteins.
4389 20373997 CD4 T cells play an important role in the immune response to this pathogen through the secretion of antiviral cytokines, and by providing help to CD8 T cells and B cells to promote the development of immunological memory and neutralizing antibody responses.
4390 20373997 In the study reported here, overlapping peptides representing 5 different influenza viral proteins were used in EliSpot assays to enumerate and identify the specificity of anti-influenza CD4 T cells directly ex vivo following infection of mice with influenza virus, using two strains that express unrelated MHC class II molecules.
4391 20373997 These experiments evaluated whether the reactivity of CD4 T cells generally tracked with particular influenza proteins, or whether MHC preferences were the predominant factor dictating anti-CD4 T-cell specificity in the primary immune response.
4392 20373997 Given the diversity of human MHC class II molecules, these findings have important implications for the ability to rationally design a vaccine that will generate a specific CD4 T-cell immune response that is effective across diverse human populations.
4393 20373997 Analyses of the specificity of CD4 T cells during the primary immune response to influenza virus reveals dramatic MHC-linked asymmetries in reactivity to individual viral proteins.
4394 20373997 CD4 T cells play an important role in the immune response to this pathogen through the secretion of antiviral cytokines, and by providing help to CD8 T cells and B cells to promote the development of immunological memory and neutralizing antibody responses.
4395 20373997 In the study reported here, overlapping peptides representing 5 different influenza viral proteins were used in EliSpot assays to enumerate and identify the specificity of anti-influenza CD4 T cells directly ex vivo following infection of mice with influenza virus, using two strains that express unrelated MHC class II molecules.
4396 20373997 These experiments evaluated whether the reactivity of CD4 T cells generally tracked with particular influenza proteins, or whether MHC preferences were the predominant factor dictating anti-CD4 T-cell specificity in the primary immune response.
4397 20373997 Given the diversity of human MHC class II molecules, these findings have important implications for the ability to rationally design a vaccine that will generate a specific CD4 T-cell immune response that is effective across diverse human populations.
4398 20373997 Analyses of the specificity of CD4 T cells during the primary immune response to influenza virus reveals dramatic MHC-linked asymmetries in reactivity to individual viral proteins.
4399 20373997 CD4 T cells play an important role in the immune response to this pathogen through the secretion of antiviral cytokines, and by providing help to CD8 T cells and B cells to promote the development of immunological memory and neutralizing antibody responses.
4400 20373997 In the study reported here, overlapping peptides representing 5 different influenza viral proteins were used in EliSpot assays to enumerate and identify the specificity of anti-influenza CD4 T cells directly ex vivo following infection of mice with influenza virus, using two strains that express unrelated MHC class II molecules.
4401 20373997 These experiments evaluated whether the reactivity of CD4 T cells generally tracked with particular influenza proteins, or whether MHC preferences were the predominant factor dictating anti-CD4 T-cell specificity in the primary immune response.
4402 20373997 Given the diversity of human MHC class II molecules, these findings have important implications for the ability to rationally design a vaccine that will generate a specific CD4 T-cell immune response that is effective across diverse human populations.
4403 20375244 Oral immunizations of HLA-A*0201 transgenic mice with recombinant SL3261 strains encoding NY-ESO-1 p157-165 or p157-167 induced NY-ESO-1 p157-165-specific CD8(+) T cells, detected by an HLA-A*0201 pentamer, and induced a T-cell response detected by an enzyme-linked immunospot assay.
4404 20379710 The method integrates predictions of proteasomal cleavage, transporter associated with antigen processing (TAP) transport efficiency, and MHC class I binding affinity into a MHC class I pathway likelihood score and is an improved and extended version of NetCTL.
4405 20396963 The highly polymorphic porcine major histocompatibility complex (MHC), or the swine leukocyte antigens (SLA), has been repeatedly associated with variations in swine immune response to pathogens and vaccines as well as with production traits.
4406 20396963 In this study, 115 animals derived from three generations of the Korean native pigs were genotyped for three SLA class I (SLA-2, SLA-3 and SLA-1) and three SLA class II loci (DRB1, DQB1, DQA) using PCR with sequence-specific primers (PCR-SSP) at the allele group resolution.
4407 20421879 To define the T-cell response to heterologous serotypes, we isolated HLA-A(*)1101-restricted epitope-specific CD8(+) T-cell lines from primary DENV-immune donors.
4408 20422411 We have identified a survivin peptide mimic containing human MHC class I epitopes and a potential class II ligand that induces a potent antitumor response in C57BL/6 mice with GL261 cerebral gliomas.
4409 20422411 We evaluated survivin peptides with predicted binding to human HLA-A*0201 antigen using peptide-loaded dendritic cells from PBMC of patients with these malignancies.
4410 20422411 We have identified a survivin peptide mimic containing human MHC class I epitopes and a potential class II ligand that induces a potent antitumor response in C57BL/6 mice with GL261 cerebral gliomas.
4411 20422411 We evaluated survivin peptides with predicted binding to human HLA-A*0201 antigen using peptide-loaded dendritic cells from PBMC of patients with these malignancies.
4412 20430956 Processing and cross-presentation of individual HLA-A, -B, or -C epitopes from NY-ESO-1 or an HLA-A epitope for Melan-A differ according to the mode of antigen delivery.
4413 20430956 We studied cross-presentation of the cancer/testis antigen, NY-ESO-1, and the melanoma differentiation antigen, Melan-A by human DC subsets.
4414 20430956 HLA-A2 epitope generation required endosomal acidification and was proteasome-independent for NY-ESO-1 and proteasome-dependent for Melan-A.
4415 20430956 Both MoDCs and CD1c(+) blood DCs cross-presented NY-ESO-1-specific HLA-A2(157-165)-, HLA-B7(60-72)-, and HLA-Cw3(92-100)-restricted epitopes when formulated as an NY-ESO-1/ISCOMATRIX vaccine, but this was limited when NY-ESO-1 and ISCOMATRIX adjuvant were added separately to the DC cultures.
4416 20439916 Our previous studies have demonstrated that the natural chaperone complexes of full-length tumor protein Ags (e.g., gp100) and large stress proteins (e.g., hsp110 and grp170) with exceptional Ag-holding capabilities augment potent tumor protective immunity.
4417 20439916 Immunization with hsp110- or grp170-tyrosinase-related protein 2 (TRP2(175-192)) peptide complexes effectively primed CD8(+) T cells reactive with TRP2-derived, MHC class I-restricted epitope.
4418 20439916 Furthermore, immunization with combined chaperone vaccines directed against two melanoma protein Ags (i.e., gp100 and TRP2) significantly improved overall anti-tumor efficacy when compared with either of the single Ag vaccine.
4419 20442757 The immune system is engaged in a constant antigenic surveillance through the Major Histocompatibility Complex (MHC) class I antigen presentation pathway.
4420 20445345 Efficacy of vaccine was tested in immunized HLA-A*0201/H2Dd transgenic mice by measuring the frequency of IFN-gamma secreting cells in the draining lymph nodes, and regulatory T-cell frequencies in the spleen.
4421 20445345 Compared with a water-in-oil emulsion vaccine, DPX-0907 enhanced IFN-gamma+CD8+ T cells in vaccine site-draining lymph nodes, as seen by immunofluorescence staining and increased the frequency of IFN-gamma+ lymph node cells as seen by enzyme-linked immunosorbent spot assay.
4422 20445345 Notably, while conventional vaccine formulations elicited elevated levels of splenic Foxp3+CD4+ and IL10-secreting T cells, this was not the case for DPX-0907-based vaccines, with treated animals exhibiting normal levels of regulatory T cells.
4423 20473949 MHC II lung cancer vaccines prime and boost tumor-specific CD4+ T cells that cross-react with multiple histologic subtypes of nonsmall cell lung cancer cells.
4424 20473949 Our vaccine strategy has focused on activating tumor-specific CD4(+) T cells, a population of lymphocytes that facilitates the optimal activation of effector and memory cytotoxic CD8(+) T cells.
4425 20473949 We now report that our NSCLC MHC II vaccines prepared from adeno, squamous or large cell carcinomas each activate CD4(+) T cells that cross-react with the other NSCLC subtypes and do not react with HLA-DR-matched normal lung fibroblasts or other HLA-DR-matched nonlung tumor cells.
4426 20473949 Using MHC II NSCLC vaccines expressing the DR1, DR4, DR7 or DR15 alleles, we also demonstrate that antigens shared among the different subtypes are presented by multiple HLA-DR alleles.
4427 20473949 Therefore, MHC II NSCLC vaccines expressing a single HLA-DR allele activate NSCLC-specific CD4(+) T cells that react with the 3 major classes of NSCLC, and the antigens recognized by the activated T cells are presented by several common HLA-DR alleles, suggesting that the MHC II NSCLC vaccines are potential immunotherapeutics for a range of NSCLC patients.
4428 20473949 MHC II lung cancer vaccines prime and boost tumor-specific CD4+ T cells that cross-react with multiple histologic subtypes of nonsmall cell lung cancer cells.
4429 20473949 Our vaccine strategy has focused on activating tumor-specific CD4(+) T cells, a population of lymphocytes that facilitates the optimal activation of effector and memory cytotoxic CD8(+) T cells.
4430 20473949 We now report that our NSCLC MHC II vaccines prepared from adeno, squamous or large cell carcinomas each activate CD4(+) T cells that cross-react with the other NSCLC subtypes and do not react with HLA-DR-matched normal lung fibroblasts or other HLA-DR-matched nonlung tumor cells.
4431 20473949 Using MHC II NSCLC vaccines expressing the DR1, DR4, DR7 or DR15 alleles, we also demonstrate that antigens shared among the different subtypes are presented by multiple HLA-DR alleles.
4432 20473949 Therefore, MHC II NSCLC vaccines expressing a single HLA-DR allele activate NSCLC-specific CD4(+) T cells that react with the 3 major classes of NSCLC, and the antigens recognized by the activated T cells are presented by several common HLA-DR alleles, suggesting that the MHC II NSCLC vaccines are potential immunotherapeutics for a range of NSCLC patients.
4433 20473949 MHC II lung cancer vaccines prime and boost tumor-specific CD4+ T cells that cross-react with multiple histologic subtypes of nonsmall cell lung cancer cells.
4434 20473949 Our vaccine strategy has focused on activating tumor-specific CD4(+) T cells, a population of lymphocytes that facilitates the optimal activation of effector and memory cytotoxic CD8(+) T cells.
4435 20473949 We now report that our NSCLC MHC II vaccines prepared from adeno, squamous or large cell carcinomas each activate CD4(+) T cells that cross-react with the other NSCLC subtypes and do not react with HLA-DR-matched normal lung fibroblasts or other HLA-DR-matched nonlung tumor cells.
4436 20473949 Using MHC II NSCLC vaccines expressing the DR1, DR4, DR7 or DR15 alleles, we also demonstrate that antigens shared among the different subtypes are presented by multiple HLA-DR alleles.
4437 20473949 Therefore, MHC II NSCLC vaccines expressing a single HLA-DR allele activate NSCLC-specific CD4(+) T cells that react with the 3 major classes of NSCLC, and the antigens recognized by the activated T cells are presented by several common HLA-DR alleles, suggesting that the MHC II NSCLC vaccines are potential immunotherapeutics for a range of NSCLC patients.
4438 20473949 MHC II lung cancer vaccines prime and boost tumor-specific CD4+ T cells that cross-react with multiple histologic subtypes of nonsmall cell lung cancer cells.
4439 20473949 Our vaccine strategy has focused on activating tumor-specific CD4(+) T cells, a population of lymphocytes that facilitates the optimal activation of effector and memory cytotoxic CD8(+) T cells.
4440 20473949 We now report that our NSCLC MHC II vaccines prepared from adeno, squamous or large cell carcinomas each activate CD4(+) T cells that cross-react with the other NSCLC subtypes and do not react with HLA-DR-matched normal lung fibroblasts or other HLA-DR-matched nonlung tumor cells.
4441 20473949 Using MHC II NSCLC vaccines expressing the DR1, DR4, DR7 or DR15 alleles, we also demonstrate that antigens shared among the different subtypes are presented by multiple HLA-DR alleles.
4442 20473949 Therefore, MHC II NSCLC vaccines expressing a single HLA-DR allele activate NSCLC-specific CD4(+) T cells that react with the 3 major classes of NSCLC, and the antigens recognized by the activated T cells are presented by several common HLA-DR alleles, suggesting that the MHC II NSCLC vaccines are potential immunotherapeutics for a range of NSCLC patients.
4443 20479886 HLA class I binding 9mer peptides from influenza A virus induce CD4 T cell responses.
4444 20480161 The most common Chinese rhesus macaque MHC class I molecule shares peptide binding repertoire with the HLA-B7 supertype.
4445 20480161 These studies provide the first functional characterization of an MHC class I molecule in the context of Chinese rhesus macaques and the first instance of HLA-B7 analogy for rhesus macaques.
4446 20480161 The most common Chinese rhesus macaque MHC class I molecule shares peptide binding repertoire with the HLA-B7 supertype.
4447 20480161 These studies provide the first functional characterization of an MHC class I molecule in the context of Chinese rhesus macaques and the first instance of HLA-B7 analogy for rhesus macaques.
4448 20485848 Oxazole-modified glycopeptides that target arthritis-associated class II MHC A(q) and DR4 proteins.
4449 20485848 The glycopeptide CII259-273, a fragment from type II collagen (CII), can induce tolerance in mice susceptible to collagen-induced arthritis (CIA), which is a validated disease model for rheumatoid arthritis (RA).
4450 20485848 These glycopeptidomimetics were evaluated for binding to murine CIA-associated A(q) and human RA-associated DR4 class II major histocompatibility complex (MHC) proteins.
4451 20485848 Oxazole-modified glycopeptides that target arthritis-associated class II MHC A(q) and DR4 proteins.
4452 20485848 The glycopeptide CII259-273, a fragment from type II collagen (CII), can induce tolerance in mice susceptible to collagen-induced arthritis (CIA), which is a validated disease model for rheumatoid arthritis (RA).
4453 20485848 These glycopeptidomimetics were evaluated for binding to murine CIA-associated A(q) and human RA-associated DR4 class II major histocompatibility complex (MHC) proteins.
4454 20502628 The 40K-OMP-specific CD4(+) T cells induced by oral 40K-OMP plus CpG ODN produced both Th1 (IFN-gamma) and Th2 (IL-4) cytokines.
4455 20502628 Furthermore, increased frequencies of CD11c(+)B220(+) DCs and CD11c(+)CD11b(+) DCs with up-regulated expression of CD80, CD86, CD40 and MHC II molecules were noted in spleen, Peyer's patches and cervical lymph nodes.
4456 20542039 Allostimulation of human PBMC in vitro and in vivo immunization of Balb c mice with the HLA-A*0201 construct elicited CD4+ and CD8+ T cell proliferative responses, IgG specific antibodies in mice and in human T cell proliferation and APOBEC3G mRNA.
4457 20544273 Identification of immunodominant HLA-B7-restricted CD8+ cytotoxic T cell epitopes derived from mammaglobin-A expressed on human breast cancers.
4458 20544273 Defining CD8(+) CTL responses to HLA class I-restricted MGBA-derived epitopes assumes significance in the context of our ongoing efforts to clinically translate vaccine strategies targeting MGBA for prevention and/or treatment of human breast cancers.
4459 20544273 Further, two CD8(+) CTL cell lines generated in vitro against T2.B7 cells individually loaded with MGBA-derived candidate epitopes showed significant cytotoxic activity against MGBA B7.1, B7.3, B7.6, and B7.7.
4460 20554774 In the controls, the challenge dose (10 to 20 50% monkey infectious doses [MID(50)]) or MHC did not affect susceptibility to infection, peak viral load, or acute CD4 T-cell loss, whereas in the chronic phase of infection, the H1 haplotype correlated with a high viral load (P = 0.0280) and CD4 loss (P = 0.0343).
4461 20566893 Targeting of DEC-205 on human dendritic cells results in efficient MHC class II-restricted antigen presentation.
4462 20566893 DEC-205, a phagocytosis receptor mediating antigen uptake, is associated with CD8(+) T-cell responses in mice.
4463 20566893 Here we fused an anti-DEC-205scFv to an HLA-DP4-restricted epitope from the tumor antigen MAGE-A3, and examined the suitability and efficacy of DEC-205 to deliver a helper epitope to human monocyte-derived DCs (moDCs).
4464 20582983 WT1 vaccine was administered to HLA-A*2402-positive patients with WT1-overexpressing residual tumor despite prior conventional treatment.
4465 20600449 Here I re-examine the origins of HLA class I supertypes using the nucleotide sequences of 88 HLA-A alleles and 117 HLA-B alleles.
4466 20616724 Generation of MHC class II-peptide ligands for CD4 T-cell allorecognition of MHC class II molecules.
4467 20619457 Structures of native and affinity-enhanced WT1 epitopes bound to HLA-A*0201: implications for WT1-based cancer therapeutics.
4468 20619457 Here we determined the structures of the class I MHC molecule HLA-A*0201 bound to the native 126-134 epitope of the WT1 peptide and a recently described variant (R1Y) with improved MHC binding.
4469 20619457 Stability measurements revealed how the R1Y substitution enhances MHC binding affinity, and together with the structures suggest a strategy for engineering WT1 variants with improved MHC binding that retain the structural features of the native peptide/MHC complex.
4470 20619457 Structures of native and affinity-enhanced WT1 epitopes bound to HLA-A*0201: implications for WT1-based cancer therapeutics.
4471 20619457 Here we determined the structures of the class I MHC molecule HLA-A*0201 bound to the native 126-134 epitope of the WT1 peptide and a recently described variant (R1Y) with improved MHC binding.
4472 20619457 Stability measurements revealed how the R1Y substitution enhances MHC binding affinity, and together with the structures suggest a strategy for engineering WT1 variants with improved MHC binding that retain the structural features of the native peptide/MHC complex.
4473 20619457 Structures of native and affinity-enhanced WT1 epitopes bound to HLA-A*0201: implications for WT1-based cancer therapeutics.
4474 20619457 Here we determined the structures of the class I MHC molecule HLA-A*0201 bound to the native 126-134 epitope of the WT1 peptide and a recently described variant (R1Y) with improved MHC binding.
4475 20619457 Stability measurements revealed how the R1Y substitution enhances MHC binding affinity, and together with the structures suggest a strategy for engineering WT1 variants with improved MHC binding that retain the structural features of the native peptide/MHC complex.
4476 20631300 Clinical responses were correlated with vaccine-associated increases in WT1-specific CD8+ T cell frequencies, as detected by peptide/HLA-A*0201 tetramer staining, and elevated levels of activated natural killer cells postvaccination.
4477 20631300 Furthermore, vaccinated patients showed increased levels of WT1-specific IFN-gamma-producing CD8+ T cells and features of general immune activation.
4478 20635891 Several studies on this subject have demonstrated that, in general, solid tumor cells are able to avoid CD8(+) cytotoxic T-cell recognition by downregulating HLA class I-restricted presentation of tumor-associated antigens.
4479 20648001 Moreover, only DCs treated with SOCS-1 siRNA, and not controls, elicited strong primary in vitro responses to well-characterized HLA-A*0201-restricted Melan-A/MART-1 and human immunodeficiency virus (HIV) Gag epitopes in naive CD8(+) T cells from healthy donors.
4480 20648001 Finally, stimulation of CD8(+) T cells from HIV-seropositive subjects with SOCS1-silenced DCs resulted in an augmented polyfunctional cytotoxic T-lymphocyte (CTL) response, suggesting that SOCS-1 silencing can restore functionally compromised T cells in HIV infection.
4481 20668086 We were able to identify a panel of HLA-A*0201-restricted peptides derived from the same region of the glycoprotein precursor (GPC) of LASV (GPC spanning residues 441 to 449 [GPC(441-449)]), LCMV (GPC(447-455)), JUNV (GPC(429-437)), MACV (GPC(444-452)), GTOV (GPC(427-435)), and WWAV (GPC(428-436)) that displayed high-affinity binding to HLA-A*0201 and were recognized by CD8(+) T cells in a cross-reactive manner following LCMV infection or peptide immunization of HLA-A*0201 transgenic mice.
4482 20668086 Immunization of HLA-A*0201 mice with the Old World peptide LASV GPC(441-449) or LCMV GPC(447-455) induced high-avidity CD8(+) T-cell responses that were able to kill syngeneic target cells pulsed with either LASV GPC(441-449) or LCMV GPC(447-455) in vivo and provided significant protection against viral challenge with LCMV.
4483 20668086 We were able to identify a panel of HLA-A*0201-restricted peptides derived from the same region of the glycoprotein precursor (GPC) of LASV (GPC spanning residues 441 to 449 [GPC(441-449)]), LCMV (GPC(447-455)), JUNV (GPC(429-437)), MACV (GPC(444-452)), GTOV (GPC(427-435)), and WWAV (GPC(428-436)) that displayed high-affinity binding to HLA-A*0201 and were recognized by CD8(+) T cells in a cross-reactive manner following LCMV infection or peptide immunization of HLA-A*0201 transgenic mice.
4484 20668086 Immunization of HLA-A*0201 mice with the Old World peptide LASV GPC(441-449) or LCMV GPC(447-455) induced high-avidity CD8(+) T-cell responses that were able to kill syngeneic target cells pulsed with either LASV GPC(441-449) or LCMV GPC(447-455) in vivo and provided significant protection against viral challenge with LCMV.
4485 20686129 The bottleneck for the induction of collagen-induced arthritis in mice is the recognition of immunodominant type II collagen (CII) peptide (CII259-273) bound to the MHC class II molecule A(q).
4486 20686129 To investigate the effect of oxidation on the efficiency of immune-specific vaccination with MHC class II/glycosylated-CII peptide complexes, we used Ncf1 mutated mice.
4487 20686129 The bottleneck for the induction of collagen-induced arthritis in mice is the recognition of immunodominant type II collagen (CII) peptide (CII259-273) bound to the MHC class II molecule A(q).
4488 20686129 To investigate the effect of oxidation on the efficiency of immune-specific vaccination with MHC class II/glycosylated-CII peptide complexes, we used Ncf1 mutated mice.
4489 20709007 CD8+ T cell response in HLA-A*0201 transgenic mice is elicited by epitopes from SARS-CoV S protein.
4490 20709007 Results showed that peptide-specific CD8(+) T cells secreted IFN-γ, TNF-α and IL-2 and expressed CD107a/b on cell surface.
4491 20709007 IFN-γ(+)CD8(+) T cells and CD107a/b(+)CD8(+) T cells distributed throughout the lymphoid and non-lymphoid tissues, but the frequency of peptide-specific CD8(+) T cells was higher in lungs than in spleens and lymph nodes.
4492 20709007 Most of the HLA-A*0201 restricted peptide-specific CD8(+) T cells represented a memory subset with CD45RB(high) and CD62L(low).
4493 20709007 Taken together, these data demonstrate that immunization with SARS S DNA and HLA-A*0201 restricted peptides can elicit antigen-specific CD8(+) T cell immune responses which may have a significant implication in the long-term protection.
4494 20709007 CD8+ T cell response in HLA-A*0201 transgenic mice is elicited by epitopes from SARS-CoV S protein.
4495 20709007 Results showed that peptide-specific CD8(+) T cells secreted IFN-γ, TNF-α and IL-2 and expressed CD107a/b on cell surface.
4496 20709007 IFN-γ(+)CD8(+) T cells and CD107a/b(+)CD8(+) T cells distributed throughout the lymphoid and non-lymphoid tissues, but the frequency of peptide-specific CD8(+) T cells was higher in lungs than in spleens and lymph nodes.
4497 20709007 Most of the HLA-A*0201 restricted peptide-specific CD8(+) T cells represented a memory subset with CD45RB(high) and CD62L(low).
4498 20709007 Taken together, these data demonstrate that immunization with SARS S DNA and HLA-A*0201 restricted peptides can elicit antigen-specific CD8(+) T cell immune responses which may have a significant implication in the long-term protection.
4499 20709007 CD8+ T cell response in HLA-A*0201 transgenic mice is elicited by epitopes from SARS-CoV S protein.
4500 20709007 Results showed that peptide-specific CD8(+) T cells secreted IFN-γ, TNF-α and IL-2 and expressed CD107a/b on cell surface.
4501 20709007 IFN-γ(+)CD8(+) T cells and CD107a/b(+)CD8(+) T cells distributed throughout the lymphoid and non-lymphoid tissues, but the frequency of peptide-specific CD8(+) T cells was higher in lungs than in spleens and lymph nodes.
4502 20709007 Most of the HLA-A*0201 restricted peptide-specific CD8(+) T cells represented a memory subset with CD45RB(high) and CD62L(low).
4503 20709007 Taken together, these data demonstrate that immunization with SARS S DNA and HLA-A*0201 restricted peptides can elicit antigen-specific CD8(+) T cell immune responses which may have a significant implication in the long-term protection.
4504 20711822 Identification of HLA-A*0201-restricted cytotoxic T lymphocyte epitope from proliferating cell nuclear antigen.
4505 20711822 Proliferating cell nuclear antigen including Ki-67 and PCNA, associated with the proliferation process of the cell, seems to be an attractive new target for tumor-specific immunotherapy.
4506 20711822 In this study, we predicted seven HLA-A*0201-restricted CTL candidate epitope of Ki-67 and eight epitope of PCNA by computer algorithm SYFPEITHI, BIMAS, and IEDB_ANN.
4507 20711822 We found Ki-67((280-288)) (LQGETQLLV) had the strongest binding-affinity with HLA-A*0201.
4508 20711822 Identification of HLA-A*0201-restricted cytotoxic T lymphocyte epitope from proliferating cell nuclear antigen.
4509 20711822 Proliferating cell nuclear antigen including Ki-67 and PCNA, associated with the proliferation process of the cell, seems to be an attractive new target for tumor-specific immunotherapy.
4510 20711822 In this study, we predicted seven HLA-A*0201-restricted CTL candidate epitope of Ki-67 and eight epitope of PCNA by computer algorithm SYFPEITHI, BIMAS, and IEDB_ANN.
4511 20711822 We found Ki-67((280-288)) (LQGETQLLV) had the strongest binding-affinity with HLA-A*0201.
4512 20711822 Identification of HLA-A*0201-restricted cytotoxic T lymphocyte epitope from proliferating cell nuclear antigen.
4513 20711822 Proliferating cell nuclear antigen including Ki-67 and PCNA, associated with the proliferation process of the cell, seems to be an attractive new target for tumor-specific immunotherapy.
4514 20711822 In this study, we predicted seven HLA-A*0201-restricted CTL candidate epitope of Ki-67 and eight epitope of PCNA by computer algorithm SYFPEITHI, BIMAS, and IEDB_ANN.
4515 20711822 We found Ki-67((280-288)) (LQGETQLLV) had the strongest binding-affinity with HLA-A*0201.
4516 20719985 These new HHV-8 epitopes activated monofunctional and polyfunctional CD8(+) T cells that produced various combinations of gamma interferon, interleukin 2, tumor necrosis factor alpha, macrophage inhibitory protein 1β, and cytotoxic degranulation marker CD107a in healthy HHV-8-seropositive individuals.
4517 20719985 We were also able to detect HHV-8-specific CD8(+) T cells in peripheral blood samples using HLA A*0201 pentamer complexes for one gB epitope, one K8.1 epitope, two LANA-1 epitopes, and one K12 epitope.
4518 20806940 Crystal structures of HLA-A*0201 complexed with Melan-A/MART-1(26(27L)-35) peptidomimetics reveal conformational heterogeneity and highlight degeneracy of T cell recognition.
4519 20806940 Here, we demonstrate that antigenic peptidomimetics of the Melan-A/MART-1(26(27L)-35) melanoma antigen adopt strikingly different conformations when bound to MHC-I, highlighting the degeneracy of T cell recognition and revealing the challenges associated with mimicking native peptide conformation.
4520 20842062 These studies demonstrated that the vaccine was able to induce HLA-A*0201-restricted T-cell responses against gp100 and NY-ESO-1, detectable directly ex vivo, in HLA-A2/K-transgenic mice.
4521 20842062 The in vitro antigen presentation studies, in the absence of appropriate animal models, demonstrated that target cells infected with the vaccine construct were lysed by MAGE-1, MAGE-3 or MART-1 peptide-specific T cells.
4522 20871626 Baculovirus-infected, bone marrow-derived DCs (BMDCs) display increased surface expression of costimulatory molecules, such as CD80, CD86 and major histocompatibility complex (MHC) classes I and II, and secrete interferons and other proinflammatory cytokines.
4523 20935209 To activate naive T cells convincingly using Mycobacterium bovis bacillus Calmette-Guérin (BCG), recombinant BCG (BCG-D70M) that was deficient in urease, expressed with gene encoding the fusion of BCG-derived heat shock protein (HSP) 70 and Mycobacterium leprae-derived major membrane protein (MMP)-II, one of the immunodominant Ags of M. leprae, was newly constructed.
4524 20935209 BCG-D70M was more potent in activation of both CD4(+) and CD8(+) subsets of naive T cells than recombinant BCGs including urease-deficient BCG and BCG-70M secreting HSP70-MMP-II fusion protein.
4525 20935209 The activation of both subsets of T cells was MHC and CD86 dependent.
4526 20935209 BCG-D70M primary infection in C57BL/6 mice produced T cells responsive to in vitro secondary stimulation with MMP-II and HSP70 and more efficiently inhibited the multiplication of subsequently challenged M. leprae than vector control BCG.
4527 20935209 These results indicate that the triple combination of HSP70, MMP-II, and urease depletion may provide a useful tool for inducing better activation of naive T cells.
4528 20975916 Development of such inhibitor/vaccines would have to take into consideration the variation in amino acid sequence analyzed in this study as this could determine epitope presentation on MHC class I antigen for afferent immune response.
4529 20976198 Despite its antigenic complexity, CD8+ T cell responses induced by infection with the parasite show profound immunodominance, as exemplified by the Tp1(214-224) epitope presented by the common and functionally important MHC class I allele N*01301.
4530 21041729 MHC class I and TCR avidity control the CD8 T cell response to IL-15/IL-15Rα complex.
4531 21041729 We now show that the naive CD8 T cell response to exogenous IL-15/IL-15Rα complex is MHC class I dependent.
4532 21041729 In the absence of β2 microglobulin, naive CD8 T cells scarcely proliferated in response to IL-15/IL-15Rα complex, whereas memory cells proliferated, although to a lesser extent, compared with levels in control mice.
4533 21041729 The loss of β2m or FcRn slightly reduced the extended half-life of IL-15/IL-15Rα complex, whereas FcRn deficiency only partially reduced the naive CD8 T cell proliferative response to IL-15/IL-15Rα complex.
4534 21041729 These data suggest that IL-15/IL-15Rα complex has selective effects on Ag-activated CD8 T cells.
4535 21041729 MHC class I and TCR avidity control the CD8 T cell response to IL-15/IL-15Rα complex.
4536 21041729 We now show that the naive CD8 T cell response to exogenous IL-15/IL-15Rα complex is MHC class I dependent.
4537 21041729 In the absence of β2 microglobulin, naive CD8 T cells scarcely proliferated in response to IL-15/IL-15Rα complex, whereas memory cells proliferated, although to a lesser extent, compared with levels in control mice.
4538 21041729 The loss of β2m or FcRn slightly reduced the extended half-life of IL-15/IL-15Rα complex, whereas FcRn deficiency only partially reduced the naive CD8 T cell proliferative response to IL-15/IL-15Rα complex.
4539 21041729 These data suggest that IL-15/IL-15Rα complex has selective effects on Ag-activated CD8 T cells.
4540 21051091 We prepared mature allogeneic dendritic cells from bone marrow and then assessed their phenotype (CD80, CD83, CD86, CD1a, CD11c, CD40 and MHC II), antigen uptake and presenting abilities.
4541 21068778 Allogeneic gene-modified tumor cells (RCC-26/IL-7/CD80) as a vaccine in patients with metastatic renal cell cancer: a clinical phase-I study.
4542 21068778 Therefore, in our clinical study, 10 human leukocyte antigen (HLA)-A(*)0201(+) patients with histologically-confirmed progressive metastatic clear cell RCC were immunized repetitively over 22 weeks with 2.5-40 × 10(6) interleukin (IL)-7/CD80 cotransfected allogeneic HLA-A(*)0201(+) tumor cells (RCC26/IL-7/CD80).
4543 21068778 However, vaccination with allogeneic RCC26/IL-7/CD80 tumor cells was not able to induce TH1-polarized immune responses.
4544 21072852 Stepwise identification of HLA-A*0201-restricted CD8+ T-cell epitope peptides from herpes simplex virus type 1 genome boosted by a StepRank scheme.
4545 21080167 CD4(+) T cells contribute importantly to the antitumor T cell response, and thus, long peptides comprising CD4 and CD8 epitopes may be efficient cancer vaccines.
4546 21080167 We have previously identified an overexpressed antigen in melanoma, MELOE-1, presenting a CD8(+) T cell epitope, MELOE-1(36-44), in the HLA-A*0201 context.
4547 21080167 A T cell repertoire against this epitope is present in HLA-A*0201+ healthy subjects and melanoma patients and the adjuvant injection of TIL containing MELOE-1 specific CD8(+) T cells to melanoma patients was shown to be beneficial.
4548 21080167 In this study, we looked for CD4(+) T cell epitopes in the vicinity of the HLA-A*0201 epitope.
4549 21080167 Finally, we showed that the long peptide MELOE-1(22-46), containing the two optimal class II epitopes and the HLA-A*0201 epitope, was efficiently processed by DC to stimulate CD4(+) and CD8(+) T cell responses in vitro, making it a potential candidate for melanoma vaccination.
4550 21080167 CD4(+) T cells contribute importantly to the antitumor T cell response, and thus, long peptides comprising CD4 and CD8 epitopes may be efficient cancer vaccines.
4551 21080167 We have previously identified an overexpressed antigen in melanoma, MELOE-1, presenting a CD8(+) T cell epitope, MELOE-1(36-44), in the HLA-A*0201 context.
4552 21080167 A T cell repertoire against this epitope is present in HLA-A*0201+ healthy subjects and melanoma patients and the adjuvant injection of TIL containing MELOE-1 specific CD8(+) T cells to melanoma patients was shown to be beneficial.
4553 21080167 In this study, we looked for CD4(+) T cell epitopes in the vicinity of the HLA-A*0201 epitope.
4554 21080167 Finally, we showed that the long peptide MELOE-1(22-46), containing the two optimal class II epitopes and the HLA-A*0201 epitope, was efficiently processed by DC to stimulate CD4(+) and CD8(+) T cell responses in vitro, making it a potential candidate for melanoma vaccination.
4555 21080167 CD4(+) T cells contribute importantly to the antitumor T cell response, and thus, long peptides comprising CD4 and CD8 epitopes may be efficient cancer vaccines.
4556 21080167 We have previously identified an overexpressed antigen in melanoma, MELOE-1, presenting a CD8(+) T cell epitope, MELOE-1(36-44), in the HLA-A*0201 context.
4557 21080167 A T cell repertoire against this epitope is present in HLA-A*0201+ healthy subjects and melanoma patients and the adjuvant injection of TIL containing MELOE-1 specific CD8(+) T cells to melanoma patients was shown to be beneficial.
4558 21080167 In this study, we looked for CD4(+) T cell epitopes in the vicinity of the HLA-A*0201 epitope.
4559 21080167 Finally, we showed that the long peptide MELOE-1(22-46), containing the two optimal class II epitopes and the HLA-A*0201 epitope, was efficiently processed by DC to stimulate CD4(+) and CD8(+) T cell responses in vitro, making it a potential candidate for melanoma vaccination.
4560 21080167 CD4(+) T cells contribute importantly to the antitumor T cell response, and thus, long peptides comprising CD4 and CD8 epitopes may be efficient cancer vaccines.
4561 21080167 We have previously identified an overexpressed antigen in melanoma, MELOE-1, presenting a CD8(+) T cell epitope, MELOE-1(36-44), in the HLA-A*0201 context.
4562 21080167 A T cell repertoire against this epitope is present in HLA-A*0201+ healthy subjects and melanoma patients and the adjuvant injection of TIL containing MELOE-1 specific CD8(+) T cells to melanoma patients was shown to be beneficial.
4563 21080167 In this study, we looked for CD4(+) T cell epitopes in the vicinity of the HLA-A*0201 epitope.
4564 21080167 Finally, we showed that the long peptide MELOE-1(22-46), containing the two optimal class II epitopes and the HLA-A*0201 epitope, was efficiently processed by DC to stimulate CD4(+) and CD8(+) T cell responses in vitro, making it a potential candidate for melanoma vaccination.
4565 21093495 Our results showed that the infection of bmDCs with SA14-14-2 resulted in viral replication and upregulation of bmDC maturation marker molecules (CD40, CD80, CD83 and MHC I).
4566 21093495 SA14-14-2 infection also stimulated the production of interferon-α (IFN-α), monocyte chemoattractant protein-1 (MCP-1/CCL2), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) of bmDC.
4567 21095258 The ideal vaccine to protect against toxoplasmosis in humans would include antigens that elicit a protective T helper cell type 1 immune response, and generate long-lived IFN-γ-producing CD8(+) T cells.
4568 21095258 Immunization of HLA-A*0201 transgenic mice with these pooled peptides, with a universal CD4(+) epitope peptide called PADRE, formulated with adjuvant GLA-SE, induced CD8(+) T cell IFN-γ production and protected against parasite challenge.
4569 21106806 A small subset of human immunodeficiency virus type 1 (HIV-1)-infected, therapy-naive individuals--referred to as long-term non-progressors (LTNPs)--maintain a favourable course of infection, often being asymptomatic for many years with high CD4(+) and CD8(+) T-cell counts (>500 cells  μl(-1)) and low plasma HIV-RNA levels (<10 ,000 copies ml(-1)).
4570 21106806 Studies have also shown that some LTNPs have unique genetic advantages, including heterozygosity for the CCR5-Δ32 polymorphism, and have been found with excitatory mutations that upregulate the production of the chemokines that competitively inhibit HIV-1 binding to CCR5 or CXCR4.
4571 21106806 Lastly, immunological factors are crucial for providing LTNPs with a natural form of control, the most important being robust HIV-specific CD4(+) and CD8(+) T-cell responses that correlate with lower viral loads.
4572 21106806 Many LTNPs carry the HLA class I B57 allele that enhances presentation of antigenic peptides on the surface of infected CD4(+) cells to cytotoxic CD8(+) T cells.
4573 21115722 Nasal immunization with a fusion protein consisting of the hemagglutinin A antigenic region and the maltose-binding protein elicits CD11c(+) CD8(+) dendritic cells for induced long-term protective immunity.
4574 21115722 Analysis of cytokine responses showed that nasal administration of 25k-hagA-MBP induced antigen-specific CD4(+) T cells producing interleukin 4 (IL-4) and IL-5, but not gamma interferon (IFN-γ), in the spleen and cervical lymph nodes (CLNs).
4575 21115722 Furthermore, increased numbers of CD11c(+) CD8α(+), but not CD11c(+) CD11b(+) or CD11c(+) B220(+), dendritic cells with upregulated expression of CD80, CD86, CD40, and major histocompatibility complex class II (MHC II) molecules were noted in the spleen, CLNs, and nasopharynx-associated lymphoreticular tissues (NALT).
4576 21135172 We investigated the role of T lymphocytes in resistance to serotype (ST) 3 Streptococcus pneumoniae in an intranasal infection model in C57BL/6 (wild-type [Wt]) and CD8(+) (CD8(-/-))- and CD4(+) (MHC class II(-/-))-deficient mice.
4577 21135172 Comparison of lung chemokine/cytokine levels by Luminex and cellular recruitment by FACS in Wt mice and knockout strains revealed that CD8(-/-) and IFN-γ(-/-) mice, which had the most lethal survival phenotype, had more CD4(+)IL-17(+) T (Th17) cells, IL-17, neutrophil chemoattractants, and lung neutrophils, and fewer regulatory T cells than Wt mice.
4578 21135172 CD4(+) T cell depletion improved the survival of ST-infected CD8(-/-) mice, and survival studies in Th17-deficient mice revealed that the Th17 response was dispensable for ST3 resistance in our model.
4579 21135172 Taken together, these findings demonstrate that CD8(+) cells are required, but CD4(+) T cells are dispensable for resistance to ST3 pneumonia in mice and suggest a previously unsuspected role for CD8(+) cells in modulating the inflammatory response to ST3.
4580 21165574 Identification of HLA-A*0201/-A*2402-restricted CTL epitope-peptides derived from a novel cancer/testis antigen, MCAK, and induction of a specific antitumor immune response.
4581 21165574 To evaluate the feasibility of developing cancer immunotherapy using MCAK peptides, we studied HLA-A*0201 and *2402 as targets for CTLs in the context of HLA class I molecules.
4582 21165574 By using a peptide with a sequence of AINPELLQL (amino acid positions 63-71 in MCAK, HLA-A*0201) and FFEIYNGKL (amino acid positions 401-409 in MCAK, HLA-A*2402), CTL responses could be induced from unseparated PBMCs by stimulation of freshly isolated, peptide-pulsed PBMCs as antigen-presenting cells (APCs) and also by using interleukin-7 and keyhole limpet hemocyanin in primary culture.
4583 21165574 The induced CTLs could lyse HLA-A-*0201/*2402 colon and gastric cancer cells expressing MCAK, as well as the peptide-pulsed target cells, in an HLA class l, and CD8 restricted manner.
4584 21165574 The identification of the MCAK/HLA-A*0201 and *2402 peptides suggests the possibility of designing peptide-based immunotherapeutic approaches that might prove effective in treating patients with MCAK-positive cancer.
4585 21165574 Identification of HLA-A*0201/-A*2402-restricted CTL epitope-peptides derived from a novel cancer/testis antigen, MCAK, and induction of a specific antitumor immune response.
4586 21165574 To evaluate the feasibility of developing cancer immunotherapy using MCAK peptides, we studied HLA-A*0201 and *2402 as targets for CTLs in the context of HLA class I molecules.
4587 21165574 By using a peptide with a sequence of AINPELLQL (amino acid positions 63-71 in MCAK, HLA-A*0201) and FFEIYNGKL (amino acid positions 401-409 in MCAK, HLA-A*2402), CTL responses could be induced from unseparated PBMCs by stimulation of freshly isolated, peptide-pulsed PBMCs as antigen-presenting cells (APCs) and also by using interleukin-7 and keyhole limpet hemocyanin in primary culture.
4588 21165574 The induced CTLs could lyse HLA-A-*0201/*2402 colon and gastric cancer cells expressing MCAK, as well as the peptide-pulsed target cells, in an HLA class l, and CD8 restricted manner.
4589 21165574 The identification of the MCAK/HLA-A*0201 and *2402 peptides suggests the possibility of designing peptide-based immunotherapeutic approaches that might prove effective in treating patients with MCAK-positive cancer.
4590 21165574 Identification of HLA-A*0201/-A*2402-restricted CTL epitope-peptides derived from a novel cancer/testis antigen, MCAK, and induction of a specific antitumor immune response.
4591 21165574 To evaluate the feasibility of developing cancer immunotherapy using MCAK peptides, we studied HLA-A*0201 and *2402 as targets for CTLs in the context of HLA class I molecules.
4592 21165574 By using a peptide with a sequence of AINPELLQL (amino acid positions 63-71 in MCAK, HLA-A*0201) and FFEIYNGKL (amino acid positions 401-409 in MCAK, HLA-A*2402), CTL responses could be induced from unseparated PBMCs by stimulation of freshly isolated, peptide-pulsed PBMCs as antigen-presenting cells (APCs) and also by using interleukin-7 and keyhole limpet hemocyanin in primary culture.
4593 21165574 The induced CTLs could lyse HLA-A-*0201/*2402 colon and gastric cancer cells expressing MCAK, as well as the peptide-pulsed target cells, in an HLA class l, and CD8 restricted manner.
4594 21165574 The identification of the MCAK/HLA-A*0201 and *2402 peptides suggests the possibility of designing peptide-based immunotherapeutic approaches that might prove effective in treating patients with MCAK-positive cancer.
4595 21165574 Identification of HLA-A*0201/-A*2402-restricted CTL epitope-peptides derived from a novel cancer/testis antigen, MCAK, and induction of a specific antitumor immune response.
4596 21165574 To evaluate the feasibility of developing cancer immunotherapy using MCAK peptides, we studied HLA-A*0201 and *2402 as targets for CTLs in the context of HLA class I molecules.
4597 21165574 By using a peptide with a sequence of AINPELLQL (amino acid positions 63-71 in MCAK, HLA-A*0201) and FFEIYNGKL (amino acid positions 401-409 in MCAK, HLA-A*2402), CTL responses could be induced from unseparated PBMCs by stimulation of freshly isolated, peptide-pulsed PBMCs as antigen-presenting cells (APCs) and also by using interleukin-7 and keyhole limpet hemocyanin in primary culture.
4598 21165574 The induced CTLs could lyse HLA-A-*0201/*2402 colon and gastric cancer cells expressing MCAK, as well as the peptide-pulsed target cells, in an HLA class l, and CD8 restricted manner.
4599 21165574 The identification of the MCAK/HLA-A*0201 and *2402 peptides suggests the possibility of designing peptide-based immunotherapeutic approaches that might prove effective in treating patients with MCAK-positive cancer.
4600 21165574 Identification of HLA-A*0201/-A*2402-restricted CTL epitope-peptides derived from a novel cancer/testis antigen, MCAK, and induction of a specific antitumor immune response.
4601 21165574 To evaluate the feasibility of developing cancer immunotherapy using MCAK peptides, we studied HLA-A*0201 and *2402 as targets for CTLs in the context of HLA class I molecules.
4602 21165574 By using a peptide with a sequence of AINPELLQL (amino acid positions 63-71 in MCAK, HLA-A*0201) and FFEIYNGKL (amino acid positions 401-409 in MCAK, HLA-A*2402), CTL responses could be induced from unseparated PBMCs by stimulation of freshly isolated, peptide-pulsed PBMCs as antigen-presenting cells (APCs) and also by using interleukin-7 and keyhole limpet hemocyanin in primary culture.
4603 21165574 The induced CTLs could lyse HLA-A-*0201/*2402 colon and gastric cancer cells expressing MCAK, as well as the peptide-pulsed target cells, in an HLA class l, and CD8 restricted manner.
4604 21165574 The identification of the MCAK/HLA-A*0201 and *2402 peptides suggests the possibility of designing peptide-based immunotherapeutic approaches that might prove effective in treating patients with MCAK-positive cancer.
4605 21169544 A total of 432 M. tuberculosis peptides predicted to bind to HLA-A*0201, HLA-A*0301, and HLA-B*0702 (representing the above supertypes) were synthesized and HLA-binding affinities determined.
4606 21169544 Using HLA/peptide tetramers for the 18 most prominently recognized HLA-A*0201-binding M. tuberculosis peptides, recognition by cured TB patients' CD8(+) T cells was validated for all 18 epitopes.
4607 21169544 Intracellular cytokine staining for IFN-γ, IL-2, and TNF-α revealed mono-, dual-, as well as triple-positive CD8(+) T cells, indicating these M. tuberculosis peptide-specific CD8(+) T cells were (poly)functional.
4608 21169544 Control CMV peptide/HLA-A*0201 tetramers stained CD8(+) T cells in M. tuberculosis-infected and noninfected individuals equally, whereas Ebola peptide/HLA-A*0201 tetramers were negative.
4609 21169544 A total of 432 M. tuberculosis peptides predicted to bind to HLA-A*0201, HLA-A*0301, and HLA-B*0702 (representing the above supertypes) were synthesized and HLA-binding affinities determined.
4610 21169544 Using HLA/peptide tetramers for the 18 most prominently recognized HLA-A*0201-binding M. tuberculosis peptides, recognition by cured TB patients' CD8(+) T cells was validated for all 18 epitopes.
4611 21169544 Intracellular cytokine staining for IFN-γ, IL-2, and TNF-α revealed mono-, dual-, as well as triple-positive CD8(+) T cells, indicating these M. tuberculosis peptide-specific CD8(+) T cells were (poly)functional.
4612 21169544 Control CMV peptide/HLA-A*0201 tetramers stained CD8(+) T cells in M. tuberculosis-infected and noninfected individuals equally, whereas Ebola peptide/HLA-A*0201 tetramers were negative.
4613 21169544 A total of 432 M. tuberculosis peptides predicted to bind to HLA-A*0201, HLA-A*0301, and HLA-B*0702 (representing the above supertypes) were synthesized and HLA-binding affinities determined.
4614 21169544 Using HLA/peptide tetramers for the 18 most prominently recognized HLA-A*0201-binding M. tuberculosis peptides, recognition by cured TB patients' CD8(+) T cells was validated for all 18 epitopes.
4615 21169544 Intracellular cytokine staining for IFN-γ, IL-2, and TNF-α revealed mono-, dual-, as well as triple-positive CD8(+) T cells, indicating these M. tuberculosis peptide-specific CD8(+) T cells were (poly)functional.
4616 21169544 Control CMV peptide/HLA-A*0201 tetramers stained CD8(+) T cells in M. tuberculosis-infected and noninfected individuals equally, whereas Ebola peptide/HLA-A*0201 tetramers were negative.
4617 21175594 ADAM metallopeptidase domain 17 (ADAM17) is naturally processed through major histocompatibility complex (MHC) class I molecules and is a potential immunotherapeutic target in breast, ovarian and prostate cancers.
4618 21175594 ADAM17 is one of the several metalloproteinases that play a key role in epidermal growth factor receptor (EGFR) signalling and has recently emerged as a new therapeutic target in several tumour types.
4619 21177918 Our results show induction of FMDV-specific CD8(+) CTL killing of MHC-matched target cells in an antigen-specific manner.
4620 21187956 In order to test the transferability of the prediction method to different MHC proteins, we trained the scoring method on binding data for DRB1*0101 and used it to make predictions for multiple MHC allotypes with distinct peptide binding specificities including representatives from the other human class II MHC loci, HLA-DP and HLA-DQ, as well as for two murine allotypes.
4621 21216868 We investigated the induction and evolution of CD8(+) T cell responses to a WNV envelope epitope, which is a dominant target in naturally infected HLA-A*02-positive individuals.
4622 21216868 In the majority of donors, CD8(+) T cells were able to lyse targets expressing WNV envelope protein and produced macrophage inflammatory protein 1ß, interferon γ, and/or tumor necrosis factor α following envelope peptide stimulation.
4623 21263453 Development of an MHC class I L(d)-restricted PSA peptide-loaded tetramer for detection of PSA-specific CD8+ T cells in the mouse.
4624 21263453 A candidate major histocompatibility complex (MHC) class I PSA peptide (HPQKVTKFML(188-197)) was selected on the basis of its ability to restimulate PSA-specific CD8(+) T cells to secrete interferon-γ in our assays.
4625 21263453 The MHC class I PSA peptide demonstrated successful restimulation of CD8(+) T cells isolated from mice previously vaccinated with a PSA-encoding adenovirus tumor vaccine, with no restimulation observed in control-vaccinated mice.
4626 21263453 Development of an MHC class I L(d)-restricted PSA peptide-loaded tetramer for detection of PSA-specific CD8+ T cells in the mouse.
4627 21263453 A candidate major histocompatibility complex (MHC) class I PSA peptide (HPQKVTKFML(188-197)) was selected on the basis of its ability to restimulate PSA-specific CD8(+) T cells to secrete interferon-γ in our assays.
4628 21263453 The MHC class I PSA peptide demonstrated successful restimulation of CD8(+) T cells isolated from mice previously vaccinated with a PSA-encoding adenovirus tumor vaccine, with no restimulation observed in control-vaccinated mice.
4629 21263453 Development of an MHC class I L(d)-restricted PSA peptide-loaded tetramer for detection of PSA-specific CD8+ T cells in the mouse.
4630 21263453 A candidate major histocompatibility complex (MHC) class I PSA peptide (HPQKVTKFML(188-197)) was selected on the basis of its ability to restimulate PSA-specific CD8(+) T cells to secrete interferon-γ in our assays.
4631 21263453 The MHC class I PSA peptide demonstrated successful restimulation of CD8(+) T cells isolated from mice previously vaccinated with a PSA-encoding adenovirus tumor vaccine, with no restimulation observed in control-vaccinated mice.
4632 21270169 Unlike humans, whose CD8(+) T cell responses are restricted by a maximum of six HLA class I alleles, macaques express up to 20 distinct major histocompatibility complex class I (MHC-I) sequences.
4633 21278214 No human genetic variant reached genome-wide significance, but polymorphisms located in the major histocompatibility complex (MHC) region showed the strongest association with response to the HIV-1 Gag protein: HLA-B alleles known to be associated with differences in HIV-1 control were responsible for these associations.
4634 21304910 We analysed CD8(+) T cell responses using intracellular cytokine stain (ICS) and MHC Class I tetramer staining for a panel of MCMV-derived epitopes.
4635 21307889 Across the trial population, vaccination resulted in an expansion of effector responses to both antigens, to the human leukocyte antigen A2-restricted modified epitope, melan A ELAGIGILTV, and to a panel of MHC class I- and II-restricted epitopes.
4636 21332943 Here, we examined the efficient induction of an HTLV-1-specific CD8+ T-cell response by oligomannose-coated liposomes (OMLs) encapsulating the human leukocyte antigen (HLA)-A*0201-restricted HTLV-1 Tax-epitope (OML/Tax).
4637 21339366 However, contrary to other ER-resident heat shock proteins such as gp96, calreticulin, and ORP150, it is not clear whether tumor-derived BiP plays a role in inducing antitumor immunity.
4638 21339366 In this study, we show that the tumor-derived secreted form of BiP is capable of inducing antitumor CD8(+) T cell responses.
4639 21339366 We show that this secreted BiP is taken up by bone marrow-derived dendritic cells, and thereafter BiP-associated Ag peptide is cross-presented in association with MHC class I molecules, resulting in elicitation of an Ag-specific CD8(+) T cell response and antitumor effect.
4640 21368092 HBHA induced DC maturation in a TLR4-dependent manner, elevating expression of the surface molecules CD40, CD80, and CD86, MHC classes I and II and the proinflammatory cytokines IL-6, IL-12, IL-1β, TNF-α, and CCR7, as well as stimulating the migratory capacity of DCs in vitro and in vivo.
4641 21368092 Mechanistic investigations established that MyD88 and TRIF signaling pathways downstream of TLR4 mediated secretion of HBHA-induced proinflammatory cytokines.
4642 21368092 HBHA-treated DCs activated naïve T cells, polarized CD4(+) and CD8(+) T cells to secrete IFN-γ, and induced T-cell-mediated cytotoxicity.
4643 21368772 We searched for associations between the immunoglobulin G antibody to protective antigen (AbPA) response to Anthrax Vaccine Adsorbed (AVA) in humans, and polymorphisms at HLA class I (HLA-A, -B, and -C) and class II (HLA-DRB1, -DQA1, -DQB1, -DPB1) loci.
4644 21369988 A combination of RENCA lysates and AbOmpA up-regulated the surface expression of co-stimulatory molecules, CD80 and CD86, and the antigen presenting molecules, major histocompatibility (MHC) class I and class II, in DCs.
4645 21369988 DCs pulsed with a combination of CA9 and AbOmpA effectively secreted IL-12 but not IL-10.
4646 21369988 DCs pulsed with CA9 and AbOmpA elicited the secretion of interferon-γ and IL-2 in T cells.
4647 21378750 Hydrophobicity as a driver of MHC class I antigen processing.
4648 21383976 Increased cytotoxic capacity of HIV-specific CD8+ T-cells associated with efficient elimination of HIV-infected CD4+ T-cell targets has been shown to distinguish long-term nonprogressors (LTNP), patients with durable control over HIV replication, from those experiencing progressive disease.
4649 21383976 Here, measurements of granzyme B target cell activity and HIV-1-infected CD4+ T-cell elimination were applied for the first time to identify antiviral activities in recipients of a replication incompetent adenovirus serotype 5 (Ad5) HIV-1 recombinant vaccine and were compared with HIV-negative individuals and chronically infected patients, including a group of LTNP.
4650 21383976 Although the recall cytotoxic capacity of the CD8+ T-cells of the vaccinee group was significantly less than that of LTNP and overlapped with that of progressors, we observed significantly higher cytotoxic responses in vaccine recipients carrying the HLA class I alleles B*27, B*57 or B*58, which have been associated with immune control over HIV replication in chronic infection.
4651 21383976 These findings suggest protective HLA class I alleles might lead to better outcomes in both chronic infection and following immunization due to more efficient priming of HIV-specific CD8+ T-cell cytotoxic responses.
4652 21383976 Increased cytotoxic capacity of HIV-specific CD8+ T-cells associated with efficient elimination of HIV-infected CD4+ T-cell targets has been shown to distinguish long-term nonprogressors (LTNP), patients with durable control over HIV replication, from those experiencing progressive disease.
4653 21383976 Here, measurements of granzyme B target cell activity and HIV-1-infected CD4+ T-cell elimination were applied for the first time to identify antiviral activities in recipients of a replication incompetent adenovirus serotype 5 (Ad5) HIV-1 recombinant vaccine and were compared with HIV-negative individuals and chronically infected patients, including a group of LTNP.
4654 21383976 Although the recall cytotoxic capacity of the CD8+ T-cells of the vaccinee group was significantly less than that of LTNP and overlapped with that of progressors, we observed significantly higher cytotoxic responses in vaccine recipients carrying the HLA class I alleles B*27, B*57 or B*58, which have been associated with immune control over HIV replication in chronic infection.
4655 21383976 These findings suggest protective HLA class I alleles might lead to better outcomes in both chronic infection and following immunization due to more efficient priming of HIV-specific CD8+ T-cell cytotoxic responses.
4656 21409596 Identification of Hydroxysteroid (17β) dehydrogenase type 12 (HSD17B12) as a CD8+ T-cell-defined human tumor antigen of human carcinomas.
4657 21409596 We have identified the HSD17B12(114-122) peptide (IYDKIKTGL) as a naturally presented HLA-A*0201 (HLA-A2)-restricted CD8(+) T-cell-defined epitope.
4658 21409596 The HSD17B12(114-122) peptide, however, is poorly immunogenic in its in vitro ability to induce peptide-specific CD8(+) T cells.
4659 21409596 Acting as an "optimized peptide", a peptide (TYDKIKTGL), which is identical to the HSD17B12(114-122) peptide except for threonine at residue 1, was required for inducing in vitro the expansion of CD8(+) T-cell effectors cross-reactive against the HSD17B12(114-122) peptide.
4660 21439315 Extracellular vesicles purified from the Ag-pulsed DCs expressed surface proteins associated with DC-derived exosomes, including major histocompatibility complex proteins (MHC I and MHC II), CD80, flotillin, and heat shock protein (HSP70).
4661 21439315 Chickens immunized with pulsed DCs or exosomes exhibited (a) higher numbers of caecal tonsil and spleen cells expressing IgG and/or IgA antibodies that were reactive with E. tenella Ag, (b) greater numbers of IL-2-, IL-16-, and IFN-γ-producing cells, and (c) higher E. tenella Ag-driven cell proliferation, compared with chickens immunized with Ag in the absence of DCs or exosomes.
4662 21482733 The PTAP sequence within the p6 domain of human immunodeficiency virus type 1 Gag regulates its ubiquitination and MHC class I antigen presentation.
4663 21482733 Endogenous peptides presented by MHC class I (MHC-I) molecules are mostly derived from de novo synthesized, erroneous proteins, so-called defective ribosomal products (DRiPs), which are rapidly degraded via the ubiquitin-proteasome pathway.
4664 21482733 The PTAP sequence within the p6 domain of human immunodeficiency virus type 1 Gag regulates its ubiquitination and MHC class I antigen presentation.
4665 21482733 Endogenous peptides presented by MHC class I (MHC-I) molecules are mostly derived from de novo synthesized, erroneous proteins, so-called defective ribosomal products (DRiPs), which are rapidly degraded via the ubiquitin-proteasome pathway.
4666 21517839 We found that the CD4 T-cell response can be exceptionally diverse, depending on the allele(s) of MHC class II molecules expressed.
4667 21518758 Here, we report that the N-terminal region of tapasin, Tpn(1-87), assisted folding of peptide-HLA-A*02:01 complexes according to the identity of the peptide.
4668 21530544 Knowledge-based virtual screening of HLA-A*0201-restricted CD8+ T-cell epitope peptides from herpes simplex virus genome.
4669 21590240 Esophageal squamous cell carcinomas were found to express both MAGE-1 (4 out of 15 samples) and MAGE-3 (7 out of 15 samples) genes, by RT-PCR.
4670 21590240 Immunoblotting revealed MAGE-1 and MAGE-3 gene products in 2 and 6 out of 15 samples, respectively.
4671 21590240 Considering the high percentages of tumor cells expressing MAGE-3 antigen, the use of epitope-based vaccines could be envisaged in patients displaying appropriate HLA-class I phenotype.
4672 21604260 Using three separate peptide sequences from prostate-specific membrane antigen (PSMA) (peptides PSMA(27) , PSMA(663) , and PSMA(711) ), this vaccine design induced high levels of CD8(+) T cells against each peptide in a HLA-A(*) 0201 preclinical model.
4673 21622218 CD8-positive T cells respond to small antigenic peptide fragments presented on class I major histocompatibility complexes (MHCs).
4674 21652516 Priming of naive CD8 T cells by dendritic cells (DCs) entails both effective antigen presentation on MHC class I products and co-stimulatory signaling.
4675 21652516 To test whether it is possible to equip the resulting MHC-I complexes with an inherent ability to activate antigen-presenting cells, we engrafted the intracellular Toll/IL-1 receptor domain of mouse Toll-like receptor (TLR) 4 or TLR2 onto the peptide-β(2)m scaffold.
4676 21653669 We previously showed that upon infection of antigen-presenting cells, HSV type 1 (HSV-1) rapidly and efficiently downregulates the major histocompatibility complex class I-like antigen-presenting molecule, CD1d, and potently inhibits its recognition by CD1d-restricted natural killer T (NKT) cells.
4677 21654520 WT1 overexpression, present in 56.3% of EOC, was associated with infiltration of Tregs [odds ratio (OR), 2.7; 95% confidence interval (95% CI), 1.6-4.7; P<0.001] and up-regulation of MHC class II (OR, 2.2; 95% CI, 1.2-4.1; P=0.014).
4678 21654520 As WT1 overexpressing EOC is associated with CTL and Treg infiltration next to MHC class II up-regulation, future clinical trials should evaluate the combination of therapeutic WT1 vaccines with strategies depleting Tregs and/or up-regulating MHC class I, in an attempt to enhance clinical efficacy in EOC patients.
4679 21654520 WT1 overexpression, present in 56.3% of EOC, was associated with infiltration of Tregs [odds ratio (OR), 2.7; 95% confidence interval (95% CI), 1.6-4.7; P<0.001] and up-regulation of MHC class II (OR, 2.2; 95% CI, 1.2-4.1; P=0.014).
4680 21654520 As WT1 overexpressing EOC is associated with CTL and Treg infiltration next to MHC class II up-regulation, future clinical trials should evaluate the combination of therapeutic WT1 vaccines with strategies depleting Tregs and/or up-regulating MHC class I, in an attempt to enhance clinical efficacy in EOC patients.
4681 21669246 Intranasal inoculation of influenza virus hemagglutinin (HA) vaccine combined with St free of surfactant protein (SP)-C resulted in failure of HA vaccine delivery to dendritic cells and loss of local and systemic immune responses.
4682 21669246 The delivery of fluoresceinated HA vaccine to cultured dendritic cells was significantly enhanced by co-administration of St or synthetic adjuvant, and moderately stimulated the expression of MHC class II and CD86.
4683 21690251 Insulin epitopes recognized by diabetogenic T cell clones bind poorly to the class II I-A(g7) molecules of nonobese diabetic (NOD) mice, which results in weak agonistic activity of the peptide MHC complex.
4684 21697763 Identification of HLA-A*0201- and A*2402-restricted epitopes of mucin 5AC expressed in advanced pancreatic cancer.
4685 21705623 MHC class I-restricted CD8(+) T cells play an important role in protective immunity against mycobacteria.
4686 21705623 Immunization with 9mer or 30mer covering the p113-121 sequence combined with TLR9 agonist CpG induced HLA-A*0201-restricted, M. leprae-specific CD8(+) T cells as visualized by p113-121/HLA-A*0201 tetramers.
4687 21705623 Most CD8(+) T cells produced IFN-γ, but distinct IFN-γ(+)/TNF-α(+) populations were detected simultaneously with significant secretion of CXCL10/IFN-γ-induced protein 10, CXCL9/MIG, and VEGF.
4688 21705623 Strikingly, peptide immunization also induced high ML1419c-specific IgG levels, strongly suggesting that peptide-specific CD8(+) T cells provide help to B cells in vivo, as CD4(+) T cells were undetectable.
4689 21705623 An additional important characteristic of p113-121-specific CD8(+) T cells was their capacity for in vivo killing of p113-121-labeled, HLA-A*0201(+) splenocytes.
4690 21705623 The cytotoxic function of p113-121/HLA-A*0201-specific CD8(+) T cells extended into direct killing of splenocytes infected with live Mycobacterium smegmatis expressing ML1419c: both 9mer and 30mer induced CD8(+) T cells that reduced the number of ML1419c-expressing mycobacteria by 95%, whereas no reduction occurred using wild-type M. smegmatis.
4691 21705623 MHC class I-restricted CD8(+) T cells play an important role in protective immunity against mycobacteria.
4692 21705623 Immunization with 9mer or 30mer covering the p113-121 sequence combined with TLR9 agonist CpG induced HLA-A*0201-restricted, M. leprae-specific CD8(+) T cells as visualized by p113-121/HLA-A*0201 tetramers.
4693 21705623 Most CD8(+) T cells produced IFN-γ, but distinct IFN-γ(+)/TNF-α(+) populations were detected simultaneously with significant secretion of CXCL10/IFN-γ-induced protein 10, CXCL9/MIG, and VEGF.
4694 21705623 Strikingly, peptide immunization also induced high ML1419c-specific IgG levels, strongly suggesting that peptide-specific CD8(+) T cells provide help to B cells in vivo, as CD4(+) T cells were undetectable.
4695 21705623 An additional important characteristic of p113-121-specific CD8(+) T cells was their capacity for in vivo killing of p113-121-labeled, HLA-A*0201(+) splenocytes.
4696 21705623 The cytotoxic function of p113-121/HLA-A*0201-specific CD8(+) T cells extended into direct killing of splenocytes infected with live Mycobacterium smegmatis expressing ML1419c: both 9mer and 30mer induced CD8(+) T cells that reduced the number of ML1419c-expressing mycobacteria by 95%, whereas no reduction occurred using wild-type M. smegmatis.
4697 21705623 MHC class I-restricted CD8(+) T cells play an important role in protective immunity against mycobacteria.
4698 21705623 Immunization with 9mer or 30mer covering the p113-121 sequence combined with TLR9 agonist CpG induced HLA-A*0201-restricted, M. leprae-specific CD8(+) T cells as visualized by p113-121/HLA-A*0201 tetramers.
4699 21705623 Most CD8(+) T cells produced IFN-γ, but distinct IFN-γ(+)/TNF-α(+) populations were detected simultaneously with significant secretion of CXCL10/IFN-γ-induced protein 10, CXCL9/MIG, and VEGF.
4700 21705623 Strikingly, peptide immunization also induced high ML1419c-specific IgG levels, strongly suggesting that peptide-specific CD8(+) T cells provide help to B cells in vivo, as CD4(+) T cells were undetectable.
4701 21705623 An additional important characteristic of p113-121-specific CD8(+) T cells was their capacity for in vivo killing of p113-121-labeled, HLA-A*0201(+) splenocytes.
4702 21705623 The cytotoxic function of p113-121/HLA-A*0201-specific CD8(+) T cells extended into direct killing of splenocytes infected with live Mycobacterium smegmatis expressing ML1419c: both 9mer and 30mer induced CD8(+) T cells that reduced the number of ML1419c-expressing mycobacteria by 95%, whereas no reduction occurred using wild-type M. smegmatis.
4703 21705623 MHC class I-restricted CD8(+) T cells play an important role in protective immunity against mycobacteria.
4704 21705623 Immunization with 9mer or 30mer covering the p113-121 sequence combined with TLR9 agonist CpG induced HLA-A*0201-restricted, M. leprae-specific CD8(+) T cells as visualized by p113-121/HLA-A*0201 tetramers.
4705 21705623 Most CD8(+) T cells produced IFN-γ, but distinct IFN-γ(+)/TNF-α(+) populations were detected simultaneously with significant secretion of CXCL10/IFN-γ-induced protein 10, CXCL9/MIG, and VEGF.
4706 21705623 Strikingly, peptide immunization also induced high ML1419c-specific IgG levels, strongly suggesting that peptide-specific CD8(+) T cells provide help to B cells in vivo, as CD4(+) T cells were undetectable.
4707 21705623 An additional important characteristic of p113-121-specific CD8(+) T cells was their capacity for in vivo killing of p113-121-labeled, HLA-A*0201(+) splenocytes.
4708 21705623 The cytotoxic function of p113-121/HLA-A*0201-specific CD8(+) T cells extended into direct killing of splenocytes infected with live Mycobacterium smegmatis expressing ML1419c: both 9mer and 30mer induced CD8(+) T cells that reduced the number of ML1419c-expressing mycobacteria by 95%, whereas no reduction occurred using wild-type M. smegmatis.
4709 21710262 Binding affinity and stability assays in T2 cells showed that two native peptides, p28 and p31, and their analogues (p28-1Y9 V, p31-1Y2L) had more potent binding activity towards HLA-A*0201 molecule.
4710 21710262 The CTLs induced by these four peptides from the peripheral blood mononuclear cells (PBMCs) of HLA-A*02+ healthy donor could lyse MCF-7 breast cancer cells (HLA-A*0201+, PLAC1+) in vitro.
4711 21710262 Binding affinity and stability assays in T2 cells showed that two native peptides, p28 and p31, and their analogues (p28-1Y9 V, p31-1Y2L) had more potent binding activity towards HLA-A*0201 molecule.
4712 21710262 The CTLs induced by these four peptides from the peripheral blood mononuclear cells (PBMCs) of HLA-A*02+ healthy donor could lyse MCF-7 breast cancer cells (HLA-A*0201+, PLAC1+) in vitro.
4713 21723900 To address this issue, successive steps (attachment, transgene expression, MHC class I antigen presentation and activation of antigen-specific T lymphocytes) involved in induction of immune responses by Ad5-based vectors have been examined in CD8α(+) and CD8α(-) murine DC subsets.
4714 21723900 Thus, superior antigen expression and MHC class I display in CD8α(+) DC may contribute to preferred priming of antigen-specific CD8(+) lymphocytes by Ad5-transduced CD8α(+) DC.
4715 21723900 To address this issue, successive steps (attachment, transgene expression, MHC class I antigen presentation and activation of antigen-specific T lymphocytes) involved in induction of immune responses by Ad5-based vectors have been examined in CD8α(+) and CD8α(-) murine DC subsets.
4716 21723900 Thus, superior antigen expression and MHC class I display in CD8α(+) DC may contribute to preferred priming of antigen-specific CD8(+) lymphocytes by Ad5-transduced CD8α(+) DC.
4717 21728171 Cancer cells reacted with enhanced expression of HLA-class I, release of CXCL10, IL-6, and type I IFN as well as tumor cell apoptosis.
4718 21728171 Monocytes and monocyte-derived DCs (MoDCs) engulfed MDA-5-activated cancer cells, and subsequently upregulated HLA-class I/II and costimulatory molecules, and secreted CXCL10 and IFN-α.
4719 21728171 Cancer cells reacted with enhanced expression of HLA-class I, release of CXCL10, IL-6, and type I IFN as well as tumor cell apoptosis.
4720 21728171 Monocytes and monocyte-derived DCs (MoDCs) engulfed MDA-5-activated cancer cells, and subsequently upregulated HLA-class I/II and costimulatory molecules, and secreted CXCL10 and IFN-α.
4721 21745520 In the present study, we aimed to evaluate the immune responses of peptide-specific CD8(+) T cells induced by HLA-A*0201 restricted severe acute respiratory syndrome-associated coronavirus (SARS-CoV) S epitopes plus CpG oligodeoxynucleotide (CpG ODN), PolyI:C and R848 as adjuvants.
4722 21745520 Our results showed that antigen specific CD8(+) T cells were elicited by HLA-A*0201 restricted SARS-CoV S epitopes.
4723 21745520 Results also demonstrated that the HLA-A*0201 restricted peptide-specific CD8(+) T cells induced by peptides plus CpG ODN carried a memory cell phenotype with CD45RB(+) and CD62L(-) and possessed long-term survival ability in vivo.
4724 21745520 In the present study, we aimed to evaluate the immune responses of peptide-specific CD8(+) T cells induced by HLA-A*0201 restricted severe acute respiratory syndrome-associated coronavirus (SARS-CoV) S epitopes plus CpG oligodeoxynucleotide (CpG ODN), PolyI:C and R848 as adjuvants.
4725 21745520 Our results showed that antigen specific CD8(+) T cells were elicited by HLA-A*0201 restricted SARS-CoV S epitopes.
4726 21745520 Results also demonstrated that the HLA-A*0201 restricted peptide-specific CD8(+) T cells induced by peptides plus CpG ODN carried a memory cell phenotype with CD45RB(+) and CD62L(-) and possessed long-term survival ability in vivo.
4727 21745520 In the present study, we aimed to evaluate the immune responses of peptide-specific CD8(+) T cells induced by HLA-A*0201 restricted severe acute respiratory syndrome-associated coronavirus (SARS-CoV) S epitopes plus CpG oligodeoxynucleotide (CpG ODN), PolyI:C and R848 as adjuvants.
4728 21745520 Our results showed that antigen specific CD8(+) T cells were elicited by HLA-A*0201 restricted SARS-CoV S epitopes.
4729 21745520 Results also demonstrated that the HLA-A*0201 restricted peptide-specific CD8(+) T cells induced by peptides plus CpG ODN carried a memory cell phenotype with CD45RB(+) and CD62L(-) and possessed long-term survival ability in vivo.
4730 21746857 A Salmonella vector vaccine expressing the saliva-binding region (SBR) of the adhesin AgI/II of Streptococcus mutans has been shown to induce a mixed Th1/Th2 anti-SBR immune response in mice and to require Toll-like receptor 2 (TLR2), TLR4, and MyD88 signaling for the induction of mucosal anti-SBR antibody responses.
4731 21746857 Bone marrow-derived DC from wild-type and TLR2, TLR4, and MyD88 knockout mice were stimulated with Salmonella vector BRD509, the SBR-expressing Salmonella vector vaccine BRD509(pSBRT7), or SBR protein, and the DC responses to different stimuli were compared by assessing costimulatory molecule expression, cytokine production, and signaling pathways.
4732 21746857 BRD509(pSBRT7) and BRD509 induced upregulation of CD80, CD86, CD40, and major histocompatibility complex class II (MHC II) expression.
4733 21746857 The low IL-12p40 and high IL-6 cytokine profile expressed by BRD509(pSBRT7)-stimulated DC may represent a shift toward a Th2 response, as suggested by the increased expression in Jagged-1.
4734 21778700 Gag-VLPs efficiently activated human monocyte-derived dendritic cells (MDDCs), eliciting MDDC maturation with an associated increase in the surface expression of CD80, CD86 and MHC classes I and II, MDDC proliferation and proinflammatory cytokine production.
4735 21805091 The tests have been carried out on comparatively large Human leukocyte antigen (HLA)-A and HLA-B allele peptide three binding datasets extracted from the Immune epitope database and analysis resource.
4736 21810614 The immunodominant CD8 T cell response to the human cytomegalovirus tegument phosphoprotein pp65(495-503) epitope critically depends on CD4 T cell help in vaccinated HLA-A*0201 transgenic mice.
4737 21810614 We evaluated in I-A(b+)/A2-HHD-II and HLA-DR1(+)/A2-DR1 mice the HLA-A*0201-restricted, multispecific CD8 T cell responses to the human CMV tegument phosphoprotein pp65 (pp65) Ag.
4738 21810614 The immunodominant e6-specific (but not the e3- and e8-specific) CD8 T cell response critically depends on CD4 T cell help.
4739 21810614 Codelivering the antigenic peptides with different heterologous CD4 T cell helper epitopes enhanced e6-specific (but not e3- or e8-specific) CD8 T cell responses.
4740 21810614 Similarly, homologous CD4 T cell help, located within an overlapping (nested) pp65(487-503) domain, facilitated induction of e6-specific CD8 T cell responses by peptide-based vaccination.
4741 21810614 The immunodominant CD8 T cell response to the human cytomegalovirus tegument phosphoprotein pp65(495-503) epitope critically depends on CD4 T cell help in vaccinated HLA-A*0201 transgenic mice.
4742 21810614 We evaluated in I-A(b+)/A2-HHD-II and HLA-DR1(+)/A2-DR1 mice the HLA-A*0201-restricted, multispecific CD8 T cell responses to the human CMV tegument phosphoprotein pp65 (pp65) Ag.
4743 21810614 The immunodominant e6-specific (but not the e3- and e8-specific) CD8 T cell response critically depends on CD4 T cell help.
4744 21810614 Codelivering the antigenic peptides with different heterologous CD4 T cell helper epitopes enhanced e6-specific (but not e3- or e8-specific) CD8 T cell responses.
4745 21810614 Similarly, homologous CD4 T cell help, located within an overlapping (nested) pp65(487-503) domain, facilitated induction of e6-specific CD8 T cell responses by peptide-based vaccination.
4746 21821799 Allogeneic HLA-A*02-restricted WT1-specific T cells from mismatched donors are highly reactive but show off-target promiscuity.
4747 21821799 T cell clones directed against the HLA-A*0201-binding WT1(126-134) peptide were generated from both HLA-A*02-positive (self-HLA-restricted) and HLA-A*02-negative [nonself (allogeneic) HLA [allo-HLA]-restricted] individuals by direct ex vivo isolation using tetramers or after in vitro priming and selection.
4748 21821799 In contrast, allo-HLA-restricted WT1 clones exhibited profound functional reactivity against a multitude of HLA-A*02-positive targets, even in the absence of exogenously loaded WT1 peptide, indicative of Ag-binding promiscuity.
4749 21821799 In contrast, the allo-HLA-restricted WT1-reactive clones recognized besides WT1 various other HLA-A*0201-binding peptides.
4750 21821799 In conclusion, allogeneic HLA-A*02-restricted WT1-specific T cells isolated from mismatched donors may be more tumor-reactive than their autologous counterparts but can show specific off-target promiscuity of potential clinical importance.
4751 21821799 Allogeneic HLA-A*02-restricted WT1-specific T cells from mismatched donors are highly reactive but show off-target promiscuity.
4752 21821799 T cell clones directed against the HLA-A*0201-binding WT1(126-134) peptide were generated from both HLA-A*02-positive (self-HLA-restricted) and HLA-A*02-negative [nonself (allogeneic) HLA [allo-HLA]-restricted] individuals by direct ex vivo isolation using tetramers or after in vitro priming and selection.
4753 21821799 In contrast, allo-HLA-restricted WT1 clones exhibited profound functional reactivity against a multitude of HLA-A*02-positive targets, even in the absence of exogenously loaded WT1 peptide, indicative of Ag-binding promiscuity.
4754 21821799 In contrast, the allo-HLA-restricted WT1-reactive clones recognized besides WT1 various other HLA-A*0201-binding peptides.
4755 21821799 In conclusion, allogeneic HLA-A*02-restricted WT1-specific T cells isolated from mismatched donors may be more tumor-reactive than their autologous counterparts but can show specific off-target promiscuity of potential clinical importance.
4756 21821799 Allogeneic HLA-A*02-restricted WT1-specific T cells from mismatched donors are highly reactive but show off-target promiscuity.
4757 21821799 T cell clones directed against the HLA-A*0201-binding WT1(126-134) peptide were generated from both HLA-A*02-positive (self-HLA-restricted) and HLA-A*02-negative [nonself (allogeneic) HLA [allo-HLA]-restricted] individuals by direct ex vivo isolation using tetramers or after in vitro priming and selection.
4758 21821799 In contrast, allo-HLA-restricted WT1 clones exhibited profound functional reactivity against a multitude of HLA-A*02-positive targets, even in the absence of exogenously loaded WT1 peptide, indicative of Ag-binding promiscuity.
4759 21821799 In contrast, the allo-HLA-restricted WT1-reactive clones recognized besides WT1 various other HLA-A*0201-binding peptides.
4760 21821799 In conclusion, allogeneic HLA-A*02-restricted WT1-specific T cells isolated from mismatched donors may be more tumor-reactive than their autologous counterparts but can show specific off-target promiscuity of potential clinical importance.
4761 21821799 Allogeneic HLA-A*02-restricted WT1-specific T cells from mismatched donors are highly reactive but show off-target promiscuity.
4762 21821799 T cell clones directed against the HLA-A*0201-binding WT1(126-134) peptide were generated from both HLA-A*02-positive (self-HLA-restricted) and HLA-A*02-negative [nonself (allogeneic) HLA [allo-HLA]-restricted] individuals by direct ex vivo isolation using tetramers or after in vitro priming and selection.
4763 21821799 In contrast, allo-HLA-restricted WT1 clones exhibited profound functional reactivity against a multitude of HLA-A*02-positive targets, even in the absence of exogenously loaded WT1 peptide, indicative of Ag-binding promiscuity.
4764 21821799 In contrast, the allo-HLA-restricted WT1-reactive clones recognized besides WT1 various other HLA-A*0201-binding peptides.
4765 21821799 In conclusion, allogeneic HLA-A*02-restricted WT1-specific T cells isolated from mismatched donors may be more tumor-reactive than their autologous counterparts but can show specific off-target promiscuity of potential clinical importance.
4766 21821799 Allogeneic HLA-A*02-restricted WT1-specific T cells from mismatched donors are highly reactive but show off-target promiscuity.
4767 21821799 T cell clones directed against the HLA-A*0201-binding WT1(126-134) peptide were generated from both HLA-A*02-positive (self-HLA-restricted) and HLA-A*02-negative [nonself (allogeneic) HLA [allo-HLA]-restricted] individuals by direct ex vivo isolation using tetramers or after in vitro priming and selection.
4768 21821799 In contrast, allo-HLA-restricted WT1 clones exhibited profound functional reactivity against a multitude of HLA-A*02-positive targets, even in the absence of exogenously loaded WT1 peptide, indicative of Ag-binding promiscuity.
4769 21821799 In contrast, the allo-HLA-restricted WT1-reactive clones recognized besides WT1 various other HLA-A*0201-binding peptides.
4770 21821799 In conclusion, allogeneic HLA-A*02-restricted WT1-specific T cells isolated from mismatched donors may be more tumor-reactive than their autologous counterparts but can show specific off-target promiscuity of potential clinical importance.
4771 21821798 Strong statistical associations between polymorphisms in HIV-1 population sequences and carriage of HLA class I alleles have been widely used to identify possible sites of CD8 T cell immune selection in vivo.
4772 21858533 Vx-001, an HLA-A*0201 restricted telomerase (TERT)-specific anti-tumor vaccine, is composed of the 9-mer cryptic TERT(572) peptide and its optimized variant TERT(572Y).
4773 21860662 Natural splice variant of MHC class I cytoplasmic tail enhances dendritic cell-induced CD8+ T-cell responses and boosts anti-tumor immunity.
4774 21868578 Donor immunization with WT1 peptide augments antileukemic activity after MHC-matched bone marrow transplantation.
4775 21868578 WT1 peptide vaccinations of healthy donor mice induced CD8(+) T cells that were specifically reactive to WT1-expressing FBL3 leukemia cells.
4776 21868578 The transfer of total CD8(+) T cells from immunized donors was more effective than the transfer of WT1-tetramer(+)CD8(+) T cells and both required CD4(+) T-cell help for maximal antitumor activity.
4777 21868578 These findings show that WT1 peptide vaccination of donor mice can dramatically enhance GvT activity after MHC-matched allogeneic BMT.
4778 21868578 Donor immunization with WT1 peptide augments antileukemic activity after MHC-matched bone marrow transplantation.
4779 21868578 WT1 peptide vaccinations of healthy donor mice induced CD8(+) T cells that were specifically reactive to WT1-expressing FBL3 leukemia cells.
4780 21868578 The transfer of total CD8(+) T cells from immunized donors was more effective than the transfer of WT1-tetramer(+)CD8(+) T cells and both required CD4(+) T-cell help for maximal antitumor activity.
4781 21868578 These findings show that WT1 peptide vaccination of donor mice can dramatically enhance GvT activity after MHC-matched allogeneic BMT.
4782 21882825 Coculture of functionalized nanoparticles with bone marrow-derived DCs significantly increased cell surface expression of MHC II, the T cell costimulatory molecules CD86 and CD40, the C-type lectin receptor CIRE and the mannose receptor CD206 over the nonfunctionalized nanoparticles.
4783 21882825 Blocking the mannose and CIRE receptors prior to the addition of functionalized nanoparticles to the culture inhibited the increased surface expression of MHC II, CD40 and CD86.
4784 21894172 Immunoglobulin light chain, Blimp-1 and cytochrome P4501B1 peptides as potential vaccines for AL amyloidosis.
4785 21894172 Three peptide/MHC I-binding algorithms identified immunogenic peptides from three AL plasma cell-associated proteins: (1) amyloidogenic λ6 light chains, (2) CYP1B1, a universal tumor antigen hyper-expressed in AL plasma cells and (3) B lymphocyte-induced maturation protein 1 (Blimp-1), a transcription factor required for plasma cell differentiation.
4786 21937447 Here we investigated the MART-1(27-35) tumor antigen, for which anchor modification (replacement of the position two alanine with leucine) dramatically reduces or ablates antigenicity with a wide range of T cell clones despite significantly improving peptide binding to MHC.
4787 21937447 We found that anchor modification in the MART-1(27-35) antigen enhances the flexibility of both the peptide and the HLA-A*0201 molecule.
4788 21937447 Here we investigated the MART-1(27-35) tumor antigen, for which anchor modification (replacement of the position two alanine with leucine) dramatically reduces or ablates antigenicity with a wide range of T cell clones despite significantly improving peptide binding to MHC.
4789 21937447 We found that anchor modification in the MART-1(27-35) antigen enhances the flexibility of both the peptide and the HLA-A*0201 molecule.
4790 21949026 MHC-independent genetic factors control the magnitude of CD4+ T cell responses to amyloid-β peptide in mice through regulatory T cell-mediated inhibition.
4791 21949026 Surprisingly, C57BL/6 mice congenic for the H-2(s) haplotype (B6.H-2(S)), which display a "permissive" MHC class II allele for presentation of the immunodominant Aβ10-24 epitope, showed a very weak CD4(+) T cell response to Aβ, suggesting that MHC-independent genes downmodulate Aβ-specific CD4(+) T cell responses in C57BL/6 background.
4792 21949026 We concluded that the magnitude of Aβ-specific CD4(+) T cell responses is critically controlled in both physiological and pathological settings by MHC-independent genetic factors that determine the overall potency of Aβ-specific Treg responses.
4793 21949026 MHC-independent genetic factors control the magnitude of CD4+ T cell responses to amyloid-β peptide in mice through regulatory T cell-mediated inhibition.
4794 21949026 Surprisingly, C57BL/6 mice congenic for the H-2(s) haplotype (B6.H-2(S)), which display a "permissive" MHC class II allele for presentation of the immunodominant Aβ10-24 epitope, showed a very weak CD4(+) T cell response to Aβ, suggesting that MHC-independent genes downmodulate Aβ-specific CD4(+) T cell responses in C57BL/6 background.
4795 21949026 We concluded that the magnitude of Aβ-specific CD4(+) T cell responses is critically controlled in both physiological and pathological settings by MHC-independent genetic factors that determine the overall potency of Aβ-specific Treg responses.
4796 21949026 MHC-independent genetic factors control the magnitude of CD4+ T cell responses to amyloid-β peptide in mice through regulatory T cell-mediated inhibition.
4797 21949026 Surprisingly, C57BL/6 mice congenic for the H-2(s) haplotype (B6.H-2(S)), which display a "permissive" MHC class II allele for presentation of the immunodominant Aβ10-24 epitope, showed a very weak CD4(+) T cell response to Aβ, suggesting that MHC-independent genes downmodulate Aβ-specific CD4(+) T cell responses in C57BL/6 background.
4798 21949026 We concluded that the magnitude of Aβ-specific CD4(+) T cell responses is critically controlled in both physiological and pathological settings by MHC-independent genetic factors that determine the overall potency of Aβ-specific Treg responses.
4799 21980478 Four out of the twenty-five 9-mer peptides tested: peptides 3 (F33-41), 13 (F214-222), 14 (F273-281), and 23 (F559-567), were found to bind to HLA-A*0201 with moderate to high affinity and were capable of inducing IFN-γ and IL-2 secretion in lymphocytes from HLA-A*0201 transgenic (HLA-Tg) mice pre-immunized with RSV or recombinant adenovirus expressing RSV F.
4800 21980478 HLA-Tg mice were immunized with these four peptides and were found to induce both Th1 and CD8+ T cell responses in in vitro secondary recall.
4801 21980478 A significant reduction of lung viral load was observed in mice immunized with peptide 23, which appeared to enhance the levels of inflammatory chemokines (CCL17, CCL22, and IL-18) but did not increase eosinophil infiltration in the lungs.
4802 21983157 The activation markers MHC-class-II, CD40, CD80 and CD86 on DCs were significantly upregulated by BCG-CS as compared to wild-type BCG (wt-BCG).
4803 21994357 Interestingly, we show that upon activation by anti-CD40 and gamma interferon (IFN-γ), B cells from PKR(-/-) mice show diminished major histocompatibility complex class II (MHC II), CD80, and CD86 levels on the cell surface compared to wild-type (WT) mice.
4804 21994357 Our data also show that PKR is necessary for optimal expression of adhesion molecules, such as CD11a and ICAM-1, that are necessary for homotypic aggregation of B cells.
4805 21994357 Furthermore, in this report we demonstrate for the first time that upon CD40 ligation, PKR is rapidly phosphorylated and activated, indicating that PKR is an early and novel downstream mediator of CD40 signaling pathways.
4806 22002320 These findings show, for the first time to our knowledge, the existence of regulatory mechanisms that direct the responding CD8(+) T-cell repertoire toward epitopes with high-stability interactions with MHC class I molecules.
4807 22019071 The results indicated that LPS strongly induced the up-regulation of some immune system genes early on in the response to treatment, including interferon (IFN)-γ, interleukin (IL)-10, and IL-1β.
4808 22019071 Furthermore, treatment with CpG ODN promoted the up-regulation of major histocompatibility complex (MHC)-II, IFN-γ and IL-10.
4809 22072744 This HESN phenotype is associated with several alleles of human leukocyte antigens (HLAs) and specific CD8(+) and CD4(+) T cell responses to HIV-1.
4810 22072744 In this study, we systematically analyzed HIV-1 clade A and D Gag CD8(+) T cell epitopes of two HLA class I alleles associated with different outcomes of HIV-1 infection.
4811 22074999 Human leukocyte antigen class I (A, B, C) and II (DRB1) diversity in the black and Caucasian South African population.
4812 22074999 A cross-section of black and Caucasian South Africans (N = 302) were genotyped at high resolution (class I HLA-A, -B, -C and class II HLA-DRB1).
4813 22074999 HLA-B, and HLA-C loci showed the strongest overall linkage disequilibrium (LD) and HLA-B/HLA-C two locus haplotypes also showed the strongest LD (D'(ij)) in both population groups.
4814 22074999 HLA-A Supertype family phenotypic frequencies did not differ between the two populations, but four (B08, B27, B58, and B62) HLA-B Supertype families differed significantly.
4815 22074999 Human leukocyte antigen class I (A, B, C) and II (DRB1) diversity in the black and Caucasian South African population.
4816 22074999 A cross-section of black and Caucasian South Africans (N = 302) were genotyped at high resolution (class I HLA-A, -B, -C and class II HLA-DRB1).
4817 22074999 HLA-B, and HLA-C loci showed the strongest overall linkage disequilibrium (LD) and HLA-B/HLA-C two locus haplotypes also showed the strongest LD (D'(ij)) in both population groups.
4818 22074999 HLA-A Supertype family phenotypic frequencies did not differ between the two populations, but four (B08, B27, B58, and B62) HLA-B Supertype families differed significantly.
4819 22074999 Human leukocyte antigen class I (A, B, C) and II (DRB1) diversity in the black and Caucasian South African population.
4820 22074999 A cross-section of black and Caucasian South Africans (N = 302) were genotyped at high resolution (class I HLA-A, -B, -C and class II HLA-DRB1).
4821 22074999 HLA-B, and HLA-C loci showed the strongest overall linkage disequilibrium (LD) and HLA-B/HLA-C two locus haplotypes also showed the strongest LD (D'(ij)) in both population groups.
4822 22074999 HLA-A Supertype family phenotypic frequencies did not differ between the two populations, but four (B08, B27, B58, and B62) HLA-B Supertype families differed significantly.
4823 22084443 Structural basis of diverse peptide accommodation by the rhesus macaque MHC class I molecule Mamu-B*17: insights into immune protection from simian immunodeficiency virus.
4824 22084443 The MHC class I molecule Mamu-B*17 has been associated with elite control of SIV infection in rhesus macaques, akin to the protective effects described for HLA-B*57 in HIV-infected individuals.
4825 22084443 In this study, we determined the crystal structures of Mamu-B*17 in complex with eight different peptides corresponding to immunodominant SIV(mac)239-derived CD8(+) T cell epitopes: HW8 (HLEVQGYW), GW10 (GSHLEVQGYW), MW9 (MHPAQTSQW), QW9 (QTSQWDDPW), FW9 (FQWMGYELW), MF8 (MRHVLEPF), IW9 (IRYPKTFGW), and IW11 (IRYPKTFGWLW).
4826 22084443 Structural basis of diverse peptide accommodation by the rhesus macaque MHC class I molecule Mamu-B*17: insights into immune protection from simian immunodeficiency virus.
4827 22084443 The MHC class I molecule Mamu-B*17 has been associated with elite control of SIV infection in rhesus macaques, akin to the protective effects described for HLA-B*57 in HIV-infected individuals.
4828 22084443 In this study, we determined the crystal structures of Mamu-B*17 in complex with eight different peptides corresponding to immunodominant SIV(mac)239-derived CD8(+) T cell epitopes: HW8 (HLEVQGYW), GW10 (GSHLEVQGYW), MW9 (MHPAQTSQW), QW9 (QTSQWDDPW), FW9 (FQWMGYELW), MF8 (MRHVLEPF), IW9 (IRYPKTFGW), and IW11 (IRYPKTFGWLW).
4829 22109656 Spontaneous antibody, and CD4 and CD8 T-cell responses against XAGE-1b (GAGED2a) in non-small cell lung cancer patients.
4830 22109656 A CD4 T-cell response was detected in 88% (14/16) and a CD8 T-cell response in 67% (6/9) in the XAGE-1b (GAGED2a) antibody-positive patients examined.
4831 22109656 Frequent antibody responses and CD4 and CD8 T-cell responses in XAGE-1b (GAGED2a) antibody-positive patients indicate the strong immunogenicity of the XAGE-1b (GAGED2a) antigen in NSCLC patients.
4832 22109656 We established T-cell clones from PBMCs of antibody-positive patients and determined the DRB1*04:05-restricted XAGE-1b (GAGED2a) 18-31 peptide (14-mer) as a CD4 T cell epitope and the A*02:06-restricted XAGE-1b (GAGED2a) 21-29 peptide (9-mer) as a CD8 T cell epitope.
4833 22109656 As for peptide recognition, CD4 and CD8 T-cell clones responded to naturally processed antigen.
4834 22109656 The CD8 T-cell clone showed cytotoxicity against a tumor expressing XAGE-1b (GAGED2a) and the appropriate HLA class I allele.
4835 22116674 Herpes simplex virus protein ICP47, encoded by US12 gene, strongly downregulates major histocompatibility complex (MHC) class-I antigen restricted presentation by blocking transporter associated with antigen processing (TAP) protein.
4836 22116674 To decrease viral vector antigenic immunodominance and MHC class-I driven clearance, we engineered recombinant vaccinia viruses (rVV) expressing ICP47 alone (rVV-US12) or together with endoplasmic reticulum (ER)-targeted Melan-A/MART-1(27-35) model tumor epitope (rVV-MUS12).
4837 22116674 In this study, we show that antigen presenting cells (APC), infected with rVV-US12, display a decreased ability to present TAP dependent MHC class-I restricted viral antigens to CD8+ T-cells.
4838 22116674 While HLA class-I cell surface expression is strongly downregulated, other important immune related molecules such as CD80, CD44 and, most importantly, MHC class-II are unaffected.
4839 22116674 Herpes simplex virus protein ICP47, encoded by US12 gene, strongly downregulates major histocompatibility complex (MHC) class-I antigen restricted presentation by blocking transporter associated with antigen processing (TAP) protein.
4840 22116674 To decrease viral vector antigenic immunodominance and MHC class-I driven clearance, we engineered recombinant vaccinia viruses (rVV) expressing ICP47 alone (rVV-US12) or together with endoplasmic reticulum (ER)-targeted Melan-A/MART-1(27-35) model tumor epitope (rVV-MUS12).
4841 22116674 In this study, we show that antigen presenting cells (APC), infected with rVV-US12, display a decreased ability to present TAP dependent MHC class-I restricted viral antigens to CD8+ T-cells.
4842 22116674 While HLA class-I cell surface expression is strongly downregulated, other important immune related molecules such as CD80, CD44 and, most importantly, MHC class-II are unaffected.
4843 22116674 Herpes simplex virus protein ICP47, encoded by US12 gene, strongly downregulates major histocompatibility complex (MHC) class-I antigen restricted presentation by blocking transporter associated with antigen processing (TAP) protein.
4844 22116674 To decrease viral vector antigenic immunodominance and MHC class-I driven clearance, we engineered recombinant vaccinia viruses (rVV) expressing ICP47 alone (rVV-US12) or together with endoplasmic reticulum (ER)-targeted Melan-A/MART-1(27-35) model tumor epitope (rVV-MUS12).
4845 22116674 In this study, we show that antigen presenting cells (APC), infected with rVV-US12, display a decreased ability to present TAP dependent MHC class-I restricted viral antigens to CD8+ T-cells.
4846 22116674 While HLA class-I cell surface expression is strongly downregulated, other important immune related molecules such as CD80, CD44 and, most importantly, MHC class-II are unaffected.
4847 22116674 Herpes simplex virus protein ICP47, encoded by US12 gene, strongly downregulates major histocompatibility complex (MHC) class-I antigen restricted presentation by blocking transporter associated with antigen processing (TAP) protein.
4848 22116674 To decrease viral vector antigenic immunodominance and MHC class-I driven clearance, we engineered recombinant vaccinia viruses (rVV) expressing ICP47 alone (rVV-US12) or together with endoplasmic reticulum (ER)-targeted Melan-A/MART-1(27-35) model tumor epitope (rVV-MUS12).
4849 22116674 In this study, we show that antigen presenting cells (APC), infected with rVV-US12, display a decreased ability to present TAP dependent MHC class-I restricted viral antigens to CD8+ T-cells.
4850 22116674 While HLA class-I cell surface expression is strongly downregulated, other important immune related molecules such as CD80, CD44 and, most importantly, MHC class-II are unaffected.
4851 22139852 IL-10 has been shown to directly affect the function of antigen-presenting cells by inhibiting the expression of MHC and costimulatory molecules, which in turn induces immune suppression or tolerance.
4852 22171012 The resultant glycopeptide epitopes can bind cell surface major histocompatibility complex (MHC) molecules and are susceptible to recognition by cytotoxic T lymphocytes (CTLs), whereas aberrantly glycosylated MUC1 protein on the tumor cell surface can be bound by antibodies to mediate antibody-dependent cell-mediated cytotoxicity (ADCC).
4853 22198310 PR1, an HLA-A*0201 epitope shared by proteinase-3 (PR3) and elastase (ELA2) proteins, is expressed in normal neutrophils and overexpressed in myeloid leukemias.
4854 22198310 We measured PR1-specific responses in 27 patients 30-120 days following allogeneic stem cell transplant (SCT) and correlated these with ELA2 and PR3 expression and minimal residual disease (MRD).
4855 22198310 Post-SCT 10/13 CML, 6/9 ALL, and 4/5 solid tumor patients had PR1 responses correlating with PR3 and ELA2 expression.
4856 22215742 The Bordetella adenylate cyclase toxin-hemolysin (CyaA; also called ACT or AC-Hly) targets CD11b-expressing phagocytes and translocates into their cytosol an adenylyl cyclase (AC) that hijacks cellular signaling by conversion of ATP to cyclic AMP (cAMP).
4857 22215742 This has repeatedly been exploited for delivery of heterologous antigens into the cytosolic pathway of CD11b-expressing dendritic cells by CyaA/AC(-) toxoids, thus enabling their processing and presentation on major histocompatibility complex (MHC) class I molecules to cytotoxic CD8(+) T lymphocytes (CTLs).
4858 22233931 CD40/APC-specific antibodies with three T-cell epitopes loaded in the constant domains induce CD4+ T-cell responses.
4859 22233931 Targeting of antigen to antigen presenting cells (APCs) increases peptide loading of major histocompatibility complex (MHC) class II molecules and CD4+ T-cell activation.
4860 22298881 Identification and immunogenicity of two new HLA-A*0201-restricted CD8+ T-cell epitopes on dengue NS1 protein.
4861 22298881 Here, we identified two new HLA-A*0201-restricted CD8(+) T-cell epitopes, DEN-4 NS1(990)(-998) and DEN-4 NS1(997)(-1005) that are conserved in three or four major DEN serotypes, respectively.
4862 22298881 Unexpectedly, we found that immunization of HLA-A*0201 transgenic mice with DEN-4 NS1(990)(-998) or DEN-4 NS1(997)(-1005) epitope peptide induced de novo synthesis of tumor necrosis factor (TNF)-α and IFN-γ, two important pro-inflammatory molecules that are hard to be detected directly without in vitro antigenic re-stimulation.
4863 22298881 Importantly, we demonstrated that CD8(+) T cells specifically activated by DEN-4 NS1(990)(-998) or DEN-4 NS1(997)(-1005) epitope peptide induced de novo synthesis of perforin.
4864 22298881 Furthermore, we observed that DEN-4 NS1(990)(-998) or DEN-4 NS1(997)(-1005)-specific CD8(+) T cells capable of producing large amounts of perforin, TNF-α and IFN-γ preferentially displayed CD27(+)CD45RA(-), but not CD27(-)CD45RA(+), phenotypes.
4865 22298881 Identification and immunogenicity of two new HLA-A*0201-restricted CD8+ T-cell epitopes on dengue NS1 protein.
4866 22298881 Here, we identified two new HLA-A*0201-restricted CD8(+) T-cell epitopes, DEN-4 NS1(990)(-998) and DEN-4 NS1(997)(-1005) that are conserved in three or four major DEN serotypes, respectively.
4867 22298881 Unexpectedly, we found that immunization of HLA-A*0201 transgenic mice with DEN-4 NS1(990)(-998) or DEN-4 NS1(997)(-1005) epitope peptide induced de novo synthesis of tumor necrosis factor (TNF)-α and IFN-γ, two important pro-inflammatory molecules that are hard to be detected directly without in vitro antigenic re-stimulation.
4868 22298881 Importantly, we demonstrated that CD8(+) T cells specifically activated by DEN-4 NS1(990)(-998) or DEN-4 NS1(997)(-1005) epitope peptide induced de novo synthesis of perforin.
4869 22298881 Furthermore, we observed that DEN-4 NS1(990)(-998) or DEN-4 NS1(997)(-1005)-specific CD8(+) T cells capable of producing large amounts of perforin, TNF-α and IFN-γ preferentially displayed CD27(+)CD45RA(-), but not CD27(-)CD45RA(+), phenotypes.
4870 22298881 Identification and immunogenicity of two new HLA-A*0201-restricted CD8+ T-cell epitopes on dengue NS1 protein.
4871 22298881 Here, we identified two new HLA-A*0201-restricted CD8(+) T-cell epitopes, DEN-4 NS1(990)(-998) and DEN-4 NS1(997)(-1005) that are conserved in three or four major DEN serotypes, respectively.
4872 22298881 Unexpectedly, we found that immunization of HLA-A*0201 transgenic mice with DEN-4 NS1(990)(-998) or DEN-4 NS1(997)(-1005) epitope peptide induced de novo synthesis of tumor necrosis factor (TNF)-α and IFN-γ, two important pro-inflammatory molecules that are hard to be detected directly without in vitro antigenic re-stimulation.
4873 22298881 Importantly, we demonstrated that CD8(+) T cells specifically activated by DEN-4 NS1(990)(-998) or DEN-4 NS1(997)(-1005) epitope peptide induced de novo synthesis of perforin.
4874 22298881 Furthermore, we observed that DEN-4 NS1(990)(-998) or DEN-4 NS1(997)(-1005)-specific CD8(+) T cells capable of producing large amounts of perforin, TNF-α and IFN-γ preferentially displayed CD27(+)CD45RA(-), but not CD27(-)CD45RA(+), phenotypes.
4875 22386748 Another reason for this may be that most peptide regimens historically have focused on activation of CD8+ cytotoxic T lymphocytes, having little or only indirect CD4+ T helper (Th) cell activation.
4876 22386748 The Ii-Key hybrid AE37, generated by linking LRMK to the known HER2 MHC class II epitope HER2 (aa 776-790), has been shown to generate robust, long lasting HER2-specific immune responses both in patients with breast and prostate cancer.
4877 22396020 Significantly elevated levels of CD3⁺ and CD8⁺ T cells as well as cells expressing interleukin (IL)-7, perforin and granulysin were found in TB lung lesions and spleen from rBCG/rAd35-vaccinated animals compared with BCG/rAd35-vaccinated or unvaccinated animals.
4878 22396020 Our observations suggest that a protective immune response in rBCG/rAd35-vaccinated nonhuman primates was associated with enhanced MHC class I antigen presentation and activation of CD8⁺ effector T-cell responses at the local site of infection in Mtb-challenged animals.
4879 22415304 Rv0577 recognizes Toll-like receptor 2 (TLR2) and functionally induces DC maturation by augmenting the expression of cell surface molecules (CD80, CD86, and MHC class I and II) and proinflammatory cytokine production (TNF-α, IL-1β, IL-6, and IL-12p70) in DCs on MyD88-dependent signaling, mitogen-activated protein kinases, and nuclear factor κB signaling pathways.
4880 22415304 In addition, Rv0577-treated DCs activated naive T cells, effectively polarized CD4(+) and CD8(+) T cells to secrete IFN-γ and IL-2, and induced T-cell proliferation, indicating that this protein possibly contributes to Th1-polarization of the immune response.
4881 22415304 More important, unlike LPS, Rv0577-treated DCs specifically induced the proliferation of memory CD4(+)/CD8(+)CD44(high)CD62L(low) T cells in the spleen of M. tuberculosis-infected mice in a TLR2-dependent manner.
4882 22418738 Peptides presented at the cell surface reflect the protein content of the cell; those on HLA class I molecules comprise the critical peptidome elements interacting with CD8 T lymphocytes.
4883 22480777 Identification of HLA-A*0201-restricted CD8+ T-cell epitope C₆₄₋₇₂ from hepatitis B virus core protein.
4884 22480777 HLA-A*0201-C₆₄₋₇₂ tetramer staining revealed the presence of a significant population of C₆₄₋₇₂-specific CTLs in C₆₄₋₇₂-stimulated CD8+ T cells.
4885 22480777 Identification of HLA-A*0201-restricted CD8+ T-cell epitope C₆₄₋₇₂ from hepatitis B virus core protein.
4886 22480777 HLA-A*0201-C₆₄₋₇₂ tetramer staining revealed the presence of a significant population of C₆₄₋₇₂-specific CTLs in C₆₄₋₇₂-stimulated CD8+ T cells.
4887 22480929 Here, we designed dendritic tandem multiple antigenic peptides (MAPs) containing the following three hTERT epitope peptides: I540, V461 and L766, which are HLA-A*02-, HLA-A*24- and HLA-RDB1*04/11/15-restricted, respectively.
4888 22484239 Cost effective and time efficient measurement of CD4, CD8, major histocompatibility complex Class II, and macrophage antigen expression in the lungs of chickens.
4889 22484239 Cells expressing CD4, CD8, major histocompatibility complex (MHC) Class II, and macrophage biomarkers in lungs of chickens were quantified by measuring total area of antigen expressed using imageJ, a software program developed at the National Institutes of Health and available at no cost.
4890 22484239 Total area of antigen expressed had positive correlation with manual counts of cells expressing CD4 and CD8 biomarkers after inoculation with serotype 1 Marek's disease virus (MDV) vaccines.
4891 22484239 Chickens infected with a very virulent+ (vv(+)) isolate of MDV (648A) had increased CD4, CD8, MHC Class II, and macrophage biomarker expression compared to noninfected control chickens at 10 days post infection, but variable responses depending on the specific biomarker measured at 3 and 5 days post infection.
4892 22484239 The procedure described here is faster and more reproducible than manual counting in cases (CD4 and CD8) where the number of positive cells is low enough for manual counts.
4893 22484239 Manual counting is not possible with MHC Class II and macrophage antigens nor when CD4(+) cells are present in large numbers following proliferation to tumors, thus subjective systems are used for scoring in these conditions.
4894 22484239 Cost effective and time efficient measurement of CD4, CD8, major histocompatibility complex Class II, and macrophage antigen expression in the lungs of chickens.
4895 22484239 Cells expressing CD4, CD8, major histocompatibility complex (MHC) Class II, and macrophage biomarkers in lungs of chickens were quantified by measuring total area of antigen expressed using imageJ, a software program developed at the National Institutes of Health and available at no cost.
4896 22484239 Total area of antigen expressed had positive correlation with manual counts of cells expressing CD4 and CD8 biomarkers after inoculation with serotype 1 Marek's disease virus (MDV) vaccines.
4897 22484239 Chickens infected with a very virulent+ (vv(+)) isolate of MDV (648A) had increased CD4, CD8, MHC Class II, and macrophage biomarker expression compared to noninfected control chickens at 10 days post infection, but variable responses depending on the specific biomarker measured at 3 and 5 days post infection.
4898 22484239 The procedure described here is faster and more reproducible than manual counting in cases (CD4 and CD8) where the number of positive cells is low enough for manual counts.
4899 22484239 Manual counting is not possible with MHC Class II and macrophage antigens nor when CD4(+) cells are present in large numbers following proliferation to tumors, thus subjective systems are used for scoring in these conditions.
4900 22484239 Cost effective and time efficient measurement of CD4, CD8, major histocompatibility complex Class II, and macrophage antigen expression in the lungs of chickens.
4901 22484239 Cells expressing CD4, CD8, major histocompatibility complex (MHC) Class II, and macrophage biomarkers in lungs of chickens were quantified by measuring total area of antigen expressed using imageJ, a software program developed at the National Institutes of Health and available at no cost.
4902 22484239 Total area of antigen expressed had positive correlation with manual counts of cells expressing CD4 and CD8 biomarkers after inoculation with serotype 1 Marek's disease virus (MDV) vaccines.
4903 22484239 Chickens infected with a very virulent+ (vv(+)) isolate of MDV (648A) had increased CD4, CD8, MHC Class II, and macrophage biomarker expression compared to noninfected control chickens at 10 days post infection, but variable responses depending on the specific biomarker measured at 3 and 5 days post infection.
4904 22484239 The procedure described here is faster and more reproducible than manual counting in cases (CD4 and CD8) where the number of positive cells is low enough for manual counts.
4905 22484239 Manual counting is not possible with MHC Class II and macrophage antigens nor when CD4(+) cells are present in large numbers following proliferation to tumors, thus subjective systems are used for scoring in these conditions.
4906 22492182 Computational prediction and experimental assessment of an HLA-A*0201-restricted cytotoxic T lymphocyte epitope from neutral endopeptidase.
4907 22492182 The CTL epitopes of NEP were screened using the long-distance prediction system SYFPEITHI and the Bioinformatics and Molecular Analysis Section of the MHC Peptide Binding Predictions program.
4908 22492182 HLA-A*0201-restricted CTL epitope NEP(375-383) can serve as a potential candidate for designing MN vaccine.
4909 22492182 Computational prediction and experimental assessment of an HLA-A*0201-restricted cytotoxic T lymphocyte epitope from neutral endopeptidase.
4910 22492182 The CTL epitopes of NEP were screened using the long-distance prediction system SYFPEITHI and the Bioinformatics and Molecular Analysis Section of the MHC Peptide Binding Predictions program.
4911 22492182 HLA-A*0201-restricted CTL epitope NEP(375-383) can serve as a potential candidate for designing MN vaccine.
4912 22492182 Computational prediction and experimental assessment of an HLA-A*0201-restricted cytotoxic T lymphocyte epitope from neutral endopeptidase.
4913 22492182 The CTL epitopes of NEP were screened using the long-distance prediction system SYFPEITHI and the Bioinformatics and Molecular Analysis Section of the MHC Peptide Binding Predictions program.
4914 22492182 HLA-A*0201-restricted CTL epitope NEP(375-383) can serve as a potential candidate for designing MN vaccine.
4915 22527248 Shikonin-tumor cell lysate-loaded mature dendritic cells exhibit a high level of CD86 and MHC class II and activate Th1 cells.
4916 22575339 Such genetic diversity has functional implications for the immune response to viruses and generates population-based variations in HLA class I allele frequencies and KIR gene profiles.
4917 22575339 Candidate gene studies of large cohorts of predominantly HIV-1 clade B but also clades C and A infected patients, have consistently shown significant associations between certain HLA class I alleles namely HLA-B*57, B*58, B*27, B*51 and relatively low viraemia.
4918 22575339 Moreover, the presence of natural killer cell receptors encoded by KIR-3DL1 and 3DS1 genes together with certain HLA class I alleles carrying the KIR target motif Bw4Ile80, provides an enhanced ability to control HIV-1 viraemia in some individuals.
4919 22575339 Such genetic diversity has functional implications for the immune response to viruses and generates population-based variations in HLA class I allele frequencies and KIR gene profiles.
4920 22575339 Candidate gene studies of large cohorts of predominantly HIV-1 clade B but also clades C and A infected patients, have consistently shown significant associations between certain HLA class I alleles namely HLA-B*57, B*58, B*27, B*51 and relatively low viraemia.
4921 22575339 Moreover, the presence of natural killer cell receptors encoded by KIR-3DL1 and 3DS1 genes together with certain HLA class I alleles carrying the KIR target motif Bw4Ile80, provides an enhanced ability to control HIV-1 viraemia in some individuals.
4922 22575339 Such genetic diversity has functional implications for the immune response to viruses and generates population-based variations in HLA class I allele frequencies and KIR gene profiles.
4923 22575339 Candidate gene studies of large cohorts of predominantly HIV-1 clade B but also clades C and A infected patients, have consistently shown significant associations between certain HLA class I alleles namely HLA-B*57, B*58, B*27, B*51 and relatively low viraemia.
4924 22575339 Moreover, the presence of natural killer cell receptors encoded by KIR-3DL1 and 3DS1 genes together with certain HLA class I alleles carrying the KIR target motif Bw4Ile80, provides an enhanced ability to control HIV-1 viraemia in some individuals.
4925 22578851 Bovine herpesvirus type 1 (BHV-1) envelope protein U(L)49.5 inhibits transporter associated with antigen processing (TAP) and down-regulates cell-surface expression of major histocompatibility complex (MHC) class I molecules to promote immune evasion.
4926 22623652 FomA induces interleukin 8 (IL-8) secretion and NF-κB-dependent luciferase activity in HEK cells expressing TLR2, IL-6 secretion, and cell surface upregulation of CD86 and major histocompatibility complex (MHC) II in primary B cells from wild-type mice, but it fails to activate cells from TLR2 knockout mice.
4927 22623652 In a mouse model of immunization with ovalbumin (OVA), FomA induces enhanced production of OVA-specific IgM and IgG, including IgG1 and IgG2b antibodies, as well as enhanced secretion of IL-10 and IL-6, consistent with a Th2-type adjuvant effect.
4928 22645177 We demonstrated that TCL1-specific CD8(+) T cells can be generated from HLA-A*0201 (HLA-A2)(+) normal donors and identified TCL1(71-78) (LLPIMWQL) as the minimal epitope recognized by these T cells.
4929 22658931 Multivariable regression modeling suggested that much of the association signal within the MHC corresponded to previously identified HLA DR-DQ haplotypes involving component HLA-DRB1 alleles of *15:01, *01:01, or *01:02.
4930 22723550 Autophagy mediates transporter associated with antigen processing-independent presentation of viral epitopes through MHC class I pathway.
4931 22723550 The endogenous presentation of the majority of viral epitopes through MHC class I pathway is strictly dependent on the transporter associated with antigen processing (TAP) complex, which transfers the peptide products of proteasomal degradation into the endoplasmic reticulum.
4932 22723550 Autophagy mediates transporter associated with antigen processing-independent presentation of viral epitopes through MHC class I pathway.
4933 22723550 The endogenous presentation of the majority of viral epitopes through MHC class I pathway is strictly dependent on the transporter associated with antigen processing (TAP) complex, which transfers the peptide products of proteasomal degradation into the endoplasmic reticulum.
4934 22729530 Induction of CD8 T-cell responses restricted to multiple HLA class I alleles in a cancer patient by immunization with a 20-mer NY-ESO-1f (NY-ESO-1 91-110) peptide.
4935 22729530 CD8 T-cell responses restricted to all five HLA class I alleles were induced in the patient after the peptide vaccination.
4936 22729530 The findings suggest the usefulness of a long 20-mer NY-ESO-1f peptide harboring multiple CD8 T-cell epitopes as an NY-ESO-1 vaccine.
4937 22729530 Induction of CD8 T-cell responses restricted to multiple HLA class I alleles in a cancer patient by immunization with a 20-mer NY-ESO-1f (NY-ESO-1 91-110) peptide.
4938 22729530 CD8 T-cell responses restricted to all five HLA class I alleles were induced in the patient after the peptide vaccination.
4939 22729530 The findings suggest the usefulness of a long 20-mer NY-ESO-1f peptide harboring multiple CD8 T-cell epitopes as an NY-ESO-1 vaccine.
4940 22735807 We have previously shown that vaccination with the natural tumor peptide Melan-A-induced T cells with superior effector functions as compared with vaccination with the analog peptide optimized for enhanced HLA-A*0201 binding.
4941 22735807 Here we found that natural peptide vaccination induced tumor-reactive CD8 T cells with frequent coexpression of both memory/homing-associated genes (CD27, IL7R, EOMES, CXCR3, and CCR5) and effector-related genes (IFNG, KLRD1, PRF1, and GZMB), comparable with protective Epstein-Barr virus-specific and cytomegalovirus-specific T cells.
4942 22761378 Depending on the source of antigen and the infectious agent, priming of CD8(+) T cells requires direct and/or cross-presentation of antigenic peptides on major histocompatibility complex (MHC) class I molecules by professional antigen-presenting cells (APCs).
4943 22761378 The long-lived nucleoprotein (NP) of lymphocytic choriomeningitis virus (LCMV) can be targeted for degradation by N-terminal fusion to ubiquitin or, as we show here, to the ubiquitin-like modifier FAT10.
4944 22778097 Previous studies in mice have focused largely on CD8(+) T cells, and the role of CD4 T cells is relatively unexplored.
4945 22778097 Here, we show that immunization of the C57BL/6 strain of mice, in which the immunodominant CD8 T cell response to the parasite dense-granule protein GRA6 cannot be generated, leads to a prominent CD4 T cell response.
4946 22778097 We isolated a cDNA encoding a protein of unknown function that we call CD4Ag28m and identified the minimal peptide, AS15, which was presented by major histocompatibility complex (MHC) class II molecules to the CD4 T cells.
4947 22815851 We use open-source epitope binding prediction programs to evaluate the binding of vaccine epitopes to Class I HLA (A, B, and C) and Class II HLA (DRB1) alleles.
4948 22860026 Strategy for identifying dendritic cell-processed CD4+ T cell epitopes from the HIV gag p24 protein.
4949 22860026 Furthermore, we demonstrated that our strategy works efficiently with HIV gag p24 protein when delivered, as vaccine protein, to Flt3L expanded mouse splenic DCs in vitro through the DEC-205 receptor.
4950 22860026 We found that the same MHC II-bound HIV gag p24 peptides, VDRFYKTLRAEQASQ and DRFYKLTRAEQASQ, were naturally processed from anti-DEC-205 HIV gag p24 protein and presented on DCs.
4951 22860026 The two identified VDRFYKTLRAEQASQ and DRFYKLTRAEQASQ MHC II-bound HIV gag p24 peptides elicited CD4(+) T-cell mediated responses in vitro.
4952 22860026 Strategy for identifying dendritic cell-processed CD4+ T cell epitopes from the HIV gag p24 protein.
4953 22860026 Furthermore, we demonstrated that our strategy works efficiently with HIV gag p24 protein when delivered, as vaccine protein, to Flt3L expanded mouse splenic DCs in vitro through the DEC-205 receptor.
4954 22860026 We found that the same MHC II-bound HIV gag p24 peptides, VDRFYKTLRAEQASQ and DRFYKLTRAEQASQ, were naturally processed from anti-DEC-205 HIV gag p24 protein and presented on DCs.
4955 22860026 The two identified VDRFYKTLRAEQASQ and DRFYKLTRAEQASQ MHC II-bound HIV gag p24 peptides elicited CD4(+) T-cell mediated responses in vitro.
4956 22875102 Anti-HIV-1 group-specific antigen (Gag) and tetanus toxoid (TTox) function improved significantly, HIV-1-associated CD8 T-cell skewing normalized, and the percentage of late-stage and major histocompatibility complex (MHC) class II expressing CD4 T-cells increased.
4957 22875102 Activated CD4(+) CD38(+) human leukocyte antigen (HLA)-DR(+) T-cells declined, and costimulation shifted to coinhibition.
4958 22914367 A major histocompatibility complex (MHC) class II antigen expression defect was found in 54% of enterovirus-positive patients and in the unique long-term poliovirus excreter.
4959 22939910 The hybrid cell lines expressed HLA class I and class II molecules, and the major T-cell costimulatory molecules, CD80 and CD86.
4960 22939910 The enhanced T-cell stimulation was inhibited by CTLA4-Ig fusion protein, and by blocking antibodies to MHC class I and class II molecules.
4961 22939910 The hybrid cell lines expressed HLA class I and class II molecules, and the major T-cell costimulatory molecules, CD80 and CD86.
4962 22939910 The enhanced T-cell stimulation was inhibited by CTLA4-Ig fusion protein, and by blocking antibodies to MHC class I and class II molecules.
4963 22942358 The major histocompatibility complex (MHC) class II-associated Invariant chain (Ii) is present in professional antigen presenting cells where it regulates peptide loading onto MHC class II molecules and the peptidome presented to CD4+ T lymphocytes.
4964 22942358 We used liquid chromatography coupled with mass spectrometry to sequence MHC II-restricted peptides from Ii+ and Ii- MCF10 human breast cancer cells transfected with HLA-DR7 or the MHC Class II transactivator CIITA to determine if Ii- cells present novel peptides.
4965 22942358 The major histocompatibility complex (MHC) class II-associated Invariant chain (Ii) is present in professional antigen presenting cells where it regulates peptide loading onto MHC class II molecules and the peptidome presented to CD4+ T lymphocytes.
4966 22942358 We used liquid chromatography coupled with mass spectrometry to sequence MHC II-restricted peptides from Ii+ and Ii- MCF10 human breast cancer cells transfected with HLA-DR7 or the MHC Class II transactivator CIITA to determine if Ii- cells present novel peptides.
4967 22970293 In this study, we have identified a novel HLA-B*1801-restricted CD8(+) T cell epitope, NY-ESO-1(88-96) (LEFYLAMPF) and compared its direct- and cross-presentation to that of the reported NY-ESO-1(157-165) epitope restricted to HLA-A*0201.
4968 22970293 On the other hand, NY-ESO-1(157-165) is efficiently presented by NY-ESO-1-expressing tumor cells and its presentation was not enhanced by IFN-γ treatment, which induced immunoproteasome as demonstrated by Western blots and functionally a decreased presentation of Melan A(26-35); whereas NY-ESO-1(88-96) was very inefficiently presented by the same tumor cell lines, except for one that expressed high level of immunoproteasome.
4969 22977597 The results indicated that the B16F10 tumor cell vaccine treated with MIT alone or in combination with reserpine (RP) and verapamil (VP) for 12 h triggered apoptosis, and that the expression of CD80, the MHC II class molecule, NKG2D and its ligand were significantly increased compared to the expression levels in the control group.
4970 22993607 To facilitate the development of a peptide-based cancer vaccine for prostate cancer patients, we examined whether any of the 13 peptides previously reported to induce HLA-class I-restricted cytotoxic T lymphocyte (CTL) activity in HLA-A3 supertype (-A3, -A11, -A31 and -A33)-positive prostate cancer patients are also capable of inducing CTLs restricted to HLA-A2, HLA-A24 or HLA-A26 alleles.
4971 22993607 The CTL activity was determined to be specific to this peptide and was mediated by CD8(+) T cells in an HLA-class I-restricted manner.
4972 22993607 To facilitate the development of a peptide-based cancer vaccine for prostate cancer patients, we examined whether any of the 13 peptides previously reported to induce HLA-class I-restricted cytotoxic T lymphocyte (CTL) activity in HLA-A3 supertype (-A3, -A11, -A31 and -A33)-positive prostate cancer patients are also capable of inducing CTLs restricted to HLA-A2, HLA-A24 or HLA-A26 alleles.
4973 22993607 The CTL activity was determined to be specific to this peptide and was mediated by CD8(+) T cells in an HLA-class I-restricted manner.
4974 23012848 To activate naïve T cells convincingly using Mycobacterium bovis BCG (BCG), rBCG (BCG-D70M) that was deficient in urease, expressed with gene encoding the fusion of BCG-derived heat shock protein (HSP) 70 and Mycobacterium leprae-derived major membrane protein (MMP)-II, one of the immunodominant Ags of M. leprae, was newly constructed.
4975 23012848 BCG-D70M was more potent in activation of both CD4+ and CD8+ subsets of naïve T cells than rBCGs including urease-deficient BCG and BCG-70M secreting HSP70-MMP-II fusion protein.
4976 23012848 The activation of both subsets of T cells was MHC and CD86 dependent.
4977 23012848 BCG-D70M primary infection in C57BL/6 mice produced T cells responsive to in vitro secondary stimulation with MMP-II and HSP70, and more efficiently inhibited the multiplication of subsequently challenged M. leprae than vector control BCG.
4978 23012848 These results indicate that the triple combination of HSP70, MMP-II and urease depletion may provide useful tool for inducing better activation of naïve T cells.
4979 23050463 In all three duck species, there was up-regulation of IFN-alpha, IFN-gamma, IL-6, CCL19, RIG-I, and MHC class I and down-regulation of MHC class II, but variable expression of IL-18 and TLR7.
4980 23084627 In addition, significantly increased transcription levels of four immune-related genes including IL-1β, MHC Iα and IIα, and IgM in the liver, spleen and kidney tissues of vaccinated fish showed that both humoral and cellular immune responses were soundly aroused in the vaccinated fish.
4981 23087058 To evaluate the relevance of directing antigen-specific CD4(+) T helper cells as part of effective anticancer immunotherapy, we investigated the immunologic and clinical responses to vaccination with dendritic cells (DC) pulsed with either MHC class I (MHC-I)-restricted epitopes alone or both MHC class I and II (MHC-I/II)-restricted epitopes.
4982 23087058 Patients received intranodal vaccinations with cytokine-matured DCs loaded with keyhole limpet hemocyanin and MHC-I alone or MHC-I/II-restricted tumor-associated antigens (TAA) of tyrosinase and gp100, depending on their HLA-DR4 status.
4983 23087058 In 4 of 15 patients vaccinated with MHC-I/II-loaded DCs and 1 of 14 patients vaccinated with MHC-I-loaded DCs, we detected TAA-specific CD8(+) T cells with maintained IFN-γ production in skin test infiltrating lymphocyte (SKIL) cultures and circulating TAA-specific CD8(+) T cells.
4984 23087058 If TAA-specific CD4(+) T-cell responses were detected in SKIL cultures, it coincided with TAA-specific CD8(+) T-cell responses.
4985 23087058 In 3 of 13 patients tested, we detected TAA-specific CD4(+)CD25(+)FoxP3(-) T cells with high proliferative capacity and IFN-γ production, indicating that these were not regulatory T cells.
4986 23087058 In conclusion, coactivating TAA-specific CD4(+) T-helper cells with DCs pulsed with both MHC class I and II-restricted epitopes augments TAA-specific CD8(+) T-cell responses, contributing to improved clinical responses.
4987 23087058 To evaluate the relevance of directing antigen-specific CD4(+) T helper cells as part of effective anticancer immunotherapy, we investigated the immunologic and clinical responses to vaccination with dendritic cells (DC) pulsed with either MHC class I (MHC-I)-restricted epitopes alone or both MHC class I and II (MHC-I/II)-restricted epitopes.
4988 23087058 Patients received intranodal vaccinations with cytokine-matured DCs loaded with keyhole limpet hemocyanin and MHC-I alone or MHC-I/II-restricted tumor-associated antigens (TAA) of tyrosinase and gp100, depending on their HLA-DR4 status.
4989 23087058 In 4 of 15 patients vaccinated with MHC-I/II-loaded DCs and 1 of 14 patients vaccinated with MHC-I-loaded DCs, we detected TAA-specific CD8(+) T cells with maintained IFN-γ production in skin test infiltrating lymphocyte (SKIL) cultures and circulating TAA-specific CD8(+) T cells.
4990 23087058 If TAA-specific CD4(+) T-cell responses were detected in SKIL cultures, it coincided with TAA-specific CD8(+) T-cell responses.
4991 23087058 In 3 of 13 patients tested, we detected TAA-specific CD4(+)CD25(+)FoxP3(-) T cells with high proliferative capacity and IFN-γ production, indicating that these were not regulatory T cells.
4992 23087058 In conclusion, coactivating TAA-specific CD4(+) T-helper cells with DCs pulsed with both MHC class I and II-restricted epitopes augments TAA-specific CD8(+) T-cell responses, contributing to improved clinical responses.
4993 23087058 To evaluate the relevance of directing antigen-specific CD4(+) T helper cells as part of effective anticancer immunotherapy, we investigated the immunologic and clinical responses to vaccination with dendritic cells (DC) pulsed with either MHC class I (MHC-I)-restricted epitopes alone or both MHC class I and II (MHC-I/II)-restricted epitopes.
4994 23087058 Patients received intranodal vaccinations with cytokine-matured DCs loaded with keyhole limpet hemocyanin and MHC-I alone or MHC-I/II-restricted tumor-associated antigens (TAA) of tyrosinase and gp100, depending on their HLA-DR4 status.
4995 23087058 In 4 of 15 patients vaccinated with MHC-I/II-loaded DCs and 1 of 14 patients vaccinated with MHC-I-loaded DCs, we detected TAA-specific CD8(+) T cells with maintained IFN-γ production in skin test infiltrating lymphocyte (SKIL) cultures and circulating TAA-specific CD8(+) T cells.
4996 23087058 If TAA-specific CD4(+) T-cell responses were detected in SKIL cultures, it coincided with TAA-specific CD8(+) T-cell responses.
4997 23087058 In 3 of 13 patients tested, we detected TAA-specific CD4(+)CD25(+)FoxP3(-) T cells with high proliferative capacity and IFN-γ production, indicating that these were not regulatory T cells.
4998 23087058 In conclusion, coactivating TAA-specific CD4(+) T-helper cells with DCs pulsed with both MHC class I and II-restricted epitopes augments TAA-specific CD8(+) T-cell responses, contributing to improved clinical responses.
4999 23105270 The ARMS-PCR technology has been found to be particularly useful for typing HLA-A, HLA-B and HLA-Cw alleles.
5000 23139801 THE SLA (swine leukocyte antigen, MHC: SLA) genes are the most important determinants of immune, infectious disease and vaccine response in pigs; several genetic associations with immunity and swine production traits have been reported.
5001 23180824 Processing of p369-377 was not detected by purified 20S proteasome and immunoproteasome, indicating that tumor cells may not be capable of processing this Ag from the HER-2/neu protein and presenting it in the context of HLA class I.
5002 23197260 Instead, we find that molecules soluble in organic solvents are dependent upon MHC class II and recognized by IFN-γ-secreting CD4(+) T cells.
5003 23225417 We have been successfully performing WT1 vaccination with a 9-mer modified WT1(235) peptide, which has one amino acid substitution (M→Y) at position 2 of 9-mer natural WT1(235) peptide (235-243 a.a.), for close to 700 HLA-A*24:02-positive patients with leukemia or solid tumors.
5004 23225417 In this study, we established a modified WT1(235) peptide-specific CTL clone, we isolated T-cell receptor (TCR) genes from it and transduced the TCR genes into CD8(+) T-cells.
5005 23225417 The TCR-transduced CD8(+) T-cells produced interferon-γ (IFNγ) and tumor necrosis factor-α (TNFα) in response to stimulation not only with the modified WT1(235) peptide but also with the natural WT1(235) peptide and lysed modified or natural WT1(235) peptide-pulsed target cells and endogenously WT1-expressing leukemia cells in a HLA-A*24:02-restriction manner.
5006 23225417 We have been successfully performing WT1 vaccination with a 9-mer modified WT1(235) peptide, which has one amino acid substitution (M→Y) at position 2 of 9-mer natural WT1(235) peptide (235-243 a.a.), for close to 700 HLA-A*24:02-positive patients with leukemia or solid tumors.
5007 23225417 In this study, we established a modified WT1(235) peptide-specific CTL clone, we isolated T-cell receptor (TCR) genes from it and transduced the TCR genes into CD8(+) T-cells.
5008 23225417 The TCR-transduced CD8(+) T-cells produced interferon-γ (IFNγ) and tumor necrosis factor-α (TNFα) in response to stimulation not only with the modified WT1(235) peptide but also with the natural WT1(235) peptide and lysed modified or natural WT1(235) peptide-pulsed target cells and endogenously WT1-expressing leukemia cells in a HLA-A*24:02-restriction manner.
5009 23226267 The cell surface receptor CD91/LRP-1 binds to immunogenic heat shock proteins (HSP) and α(2)M ligands to elicit T cell immune responses.
5010 23226267 In order to generate specific immune responses, the peptides chaperoned by HSPs or α(2)M are cross-presented on MHC molecules to T cells.
5011 23246542 Identification of novel HLA-A 0201-restricted cytotoxic T lymphocyte epitopes from Zinc Transporter 8.
5012 23246542 Zinc Transporter 8 (ZnT8) has emerged in recent years as a target of disease-associated autoreactive T cells in human T1D.
5013 23246542 However, ZnT8-associated CTL specific-peptides have not been identified.
5014 23246542 In this study, we predicted and identified HLA-A*0201-restricted cytotoxic T lymphocyte (CTL) epitopes derived from ZnT8, and utilized it to immunize HLA-A2.1/Kb transgenic (Tg) mice.
5015 23246542 The results demonstrated that peptides of ZnT8 containing residues 107-115, 115-123 and 145-153 could elicit specific CTLs in vitro, and induce diabetes in mice.
5016 23246542 Identification of novel HLA-A 0201-restricted cytotoxic T lymphocyte epitopes from Zinc Transporter 8.
5017 23246542 Zinc Transporter 8 (ZnT8) has emerged in recent years as a target of disease-associated autoreactive T cells in human T1D.
5018 23246542 However, ZnT8-associated CTL specific-peptides have not been identified.
5019 23246542 In this study, we predicted and identified HLA-A*0201-restricted cytotoxic T lymphocyte (CTL) epitopes derived from ZnT8, and utilized it to immunize HLA-A2.1/Kb transgenic (Tg) mice.
5020 23246542 The results demonstrated that peptides of ZnT8 containing residues 107-115, 115-123 and 145-153 could elicit specific CTLs in vitro, and induce diabetes in mice.
5021 23246902 Phenotypic maturation of BMDCs was confirmed by conventional scanning electron microscopy (SEM), flow cytometry (FCM) and functional maturation by transmission electron microscopy (TEM), cytochemistry assay, Acid phosphatase (ACP) activity, FITC-dextran, bio-assay and enzyme linked immunosorbent assay (ELISA).We found that RGP up-regulated the expression of CD40, CD80, CD83, CD86 and MHC II molecules of BMDCs, down-regulated pinocytosis and phagocytosis activity, induced IL-12 and TNF-α production of BMDCs.
5022 23291105 In addition, the expression levels of immune-related genes such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), major histocompatibility complexes I and II (MHC I and II), and transforming growth factor-β1 (TGF-β1) were determined in spleen and gills.
5023 23408634 BV injection also elicited BV-specific Th1 and Th2 responses as well as CD4(+) and CD8(+) T cell responses. gp64 was a primary immunogen to activate the antibody and CD8(+) T cell response, with its peptide at positions 457 to 465 (peptide 457-465) being the major histocompatibility complex (MHC) class I epitope to stimulate CD8(+) T cell and cytotoxic responses.
5024 23426430 Two novel squamous cell carcinoma antigen-derived HLA-A*0201-binding peptides induce in vitro and in vivo CD8+ cytotoxic T lymphocyte responses.
5025 23426430 In the present study, we screened the SCCA amino acid sequence for potential HLA-A*0201-binding CD8(+) T‑cell epitopes using two predictive computational algorithms.
5026 23426430 Both SCCA(328‑336) and SCCA(324-332) induced CD8(+) IFN-γ(+) T‑cell responses in HLA-A*0201-positive peripheral blood mononuclear cells as assessed by intracellular cytokine staining.
5027 23426430 Consistent with this, immunization with either SCCA(328-336) or SCCA(324‑332) effectively elicited CD8(+) IFN-γ(+) T cells in HLA-A*0201 transgenic mice as visualized by IFN-γ ELISPOT assay and intracellular cytokine staining.
5028 23426430 Two novel squamous cell carcinoma antigen-derived HLA-A*0201-binding peptides induce in vitro and in vivo CD8+ cytotoxic T lymphocyte responses.
5029 23426430 In the present study, we screened the SCCA amino acid sequence for potential HLA-A*0201-binding CD8(+) T‑cell epitopes using two predictive computational algorithms.
5030 23426430 Both SCCA(328‑336) and SCCA(324-332) induced CD8(+) IFN-γ(+) T‑cell responses in HLA-A*0201-positive peripheral blood mononuclear cells as assessed by intracellular cytokine staining.
5031 23426430 Consistent with this, immunization with either SCCA(328-336) or SCCA(324‑332) effectively elicited CD8(+) IFN-γ(+) T cells in HLA-A*0201 transgenic mice as visualized by IFN-γ ELISPOT assay and intracellular cytokine staining.
5032 23426430 Two novel squamous cell carcinoma antigen-derived HLA-A*0201-binding peptides induce in vitro and in vivo CD8+ cytotoxic T lymphocyte responses.
5033 23426430 In the present study, we screened the SCCA amino acid sequence for potential HLA-A*0201-binding CD8(+) T‑cell epitopes using two predictive computational algorithms.
5034 23426430 Both SCCA(328‑336) and SCCA(324-332) induced CD8(+) IFN-γ(+) T‑cell responses in HLA-A*0201-positive peripheral blood mononuclear cells as assessed by intracellular cytokine staining.
5035 23426430 Consistent with this, immunization with either SCCA(328-336) or SCCA(324‑332) effectively elicited CD8(+) IFN-γ(+) T cells in HLA-A*0201 transgenic mice as visualized by IFN-γ ELISPOT assay and intracellular cytokine staining.
5036 23426430 Two novel squamous cell carcinoma antigen-derived HLA-A*0201-binding peptides induce in vitro and in vivo CD8+ cytotoxic T lymphocyte responses.
5037 23426430 In the present study, we screened the SCCA amino acid sequence for potential HLA-A*0201-binding CD8(+) T‑cell epitopes using two predictive computational algorithms.
5038 23426430 Both SCCA(328‑336) and SCCA(324-332) induced CD8(+) IFN-γ(+) T‑cell responses in HLA-A*0201-positive peripheral blood mononuclear cells as assessed by intracellular cytokine staining.
5039 23426430 Consistent with this, immunization with either SCCA(328-336) or SCCA(324‑332) effectively elicited CD8(+) IFN-γ(+) T cells in HLA-A*0201 transgenic mice as visualized by IFN-γ ELISPOT assay and intracellular cytokine staining.
5040 23428979 Establishment of a stable T lymphoma cell line transduced with HLA-A*24:02-restricted WT1-specific TCR genes and its application to antigen-specific immunomonitoring.
5041 23428979 A natural 9-mer peptide (CYTWNQMNL), which bound to human leukocyte antigen (HLA)-A*24:02, was identified from among WT1-specific cytotoxic T lymphocyte (CTL) epitopes.
5042 23428979 This natural WT1 CTL epitope peptide was further modified (CMTWNQMNL) to enhance its binding affinity to HLA-A*24:02.
5043 23428979 This modified WT1 CTL epitope peptide was superior to the natural peptide for inducing HLA-A*24:02-restricted WT1-specific CTLs.
5044 23428979 Establishment of a stable T lymphoma cell line transduced with HLA-A*24:02-restricted WT1-specific TCR genes and its application to antigen-specific immunomonitoring.
5045 23428979 A natural 9-mer peptide (CYTWNQMNL), which bound to human leukocyte antigen (HLA)-A*24:02, was identified from among WT1-specific cytotoxic T lymphocyte (CTL) epitopes.
5046 23428979 This natural WT1 CTL epitope peptide was further modified (CMTWNQMNL) to enhance its binding affinity to HLA-A*24:02.
5047 23428979 This modified WT1 CTL epitope peptide was superior to the natural peptide for inducing HLA-A*24:02-restricted WT1-specific CTLs.
5048 23428979 Establishment of a stable T lymphoma cell line transduced with HLA-A*24:02-restricted WT1-specific TCR genes and its application to antigen-specific immunomonitoring.
5049 23428979 A natural 9-mer peptide (CYTWNQMNL), which bound to human leukocyte antigen (HLA)-A*24:02, was identified from among WT1-specific cytotoxic T lymphocyte (CTL) epitopes.
5050 23428979 This natural WT1 CTL epitope peptide was further modified (CMTWNQMNL) to enhance its binding affinity to HLA-A*24:02.
5051 23428979 This modified WT1 CTL epitope peptide was superior to the natural peptide for inducing HLA-A*24:02-restricted WT1-specific CTLs.
5052 23428979 Establishment of a stable T lymphoma cell line transduced with HLA-A*24:02-restricted WT1-specific TCR genes and its application to antigen-specific immunomonitoring.
5053 23428979 A natural 9-mer peptide (CYTWNQMNL), which bound to human leukocyte antigen (HLA)-A*24:02, was identified from among WT1-specific cytotoxic T lymphocyte (CTL) epitopes.
5054 23428979 This natural WT1 CTL epitope peptide was further modified (CMTWNQMNL) to enhance its binding affinity to HLA-A*24:02.
5055 23428979 This modified WT1 CTL epitope peptide was superior to the natural peptide for inducing HLA-A*24:02-restricted WT1-specific CTLs.
5056 23454300 These DCs can express CD11c, CD1b, CD5, MHC class II and CD8.
5057 23468108 While it is generally accepted that class II MHC-restricted CD4(+) T cells are essential for immunity to tuberculosis, M. tuberculosis infection elicits CD8(+) T cells responses in both people and in experimental animals.
5058 23527138 HLA-A*0201 (A2)-restricted epitopic determinants were identified with N-specific CD8(+) T cells from eight healthy donors that were primed with dendritic cells transduced to express N, and subsequently expanded in vitro by weekly re-stimulations with monocytes pulsed with 59 15mer overlapping peptides (OLPs) across N.
5059 23527138 VT9- and IL9-specific CD8(+) T cells identified by tetramer staining were cytotoxic and polyfunctional, characteristics deemed important for viral control in vivo.
5060 23562574 The effect of this stimulation regarding the transcription-pattern of the tyrosinase gene family (melanin genes) and the immune-related genes MHC class II and IFN-1 was analysed using real-time RT-qPCR.
5061 23562574 At 10°C cultivation, tyrosinase and dopachrome tautomerase remained unregulated.
5062 23589107 Effects of cyclophosphamide and IL-2 on regulatory CD4+ T cell frequency and function in melanoma patients vaccinated with HLA-class I peptides: impact on the antigen-specific T cell response.
5063 23589107 Moreover, low-dose IL-2 promoted the concomitant expansion of conventional activated CD4(+) T cells.
5064 23589107 Despite the amplification of Tregs, IL-2 administration maintained or further increased the number of antigen-specific CD8(+) T cells that were induced by vaccination as demonstrated by the ex vivo human leukocyte antigen-multimer staining and IFN-γ ELISpot assays.
5065 23589107 Despite the Treg expansion that was observed in this study, low-dose IL-2 is not detrimental to the functional activities of vaccine-primed CD8(+) T cell effectors when used in the inflammatory environment of vaccination.
5066 23637791 There is evidence to suggest a role for purified MOMP from Chlamydophila pneumoniae and corresponding MOMP-derived peptides in immune-modulation, leading to a reduced atherosclerotic phenotype in apoE(-/-) mice via a characteristic dampening of MHC class II activity.
5067 23638188 The P domain complexes induced significant central memory CD4(+) T cell phenotypes (CD4(+) CD44(+) CD62L(+) CCR7(+)) and activated polyclonal CD4(+) T cells as shown by production of Interleukin (IL)-2, Interferon (IFN)-γ, and Tumor Necrosis Factor (TNF)-α.
5068 23638188 Furthermore, P domain complexes efficiently induced bone marrow-derived dendritic cell (BMDC) maturation, evidenced by up-regulation of co-stimulatory and MHC class II molecules, as well as production of IL-12 and IL-1β.
5069 23649091 Similarly, we found that class I (HLA-A) and class II (HLA-DQA1 and HLA-DQB1) homozygosity was significantly associated with an overall decrease in LP compared with heterozygosity at those three loci.
5070 23649091 Specifically, individuals who were homozygous at these loci had significantly lower PA-specific LP than subjects heterozygous for HLA-A (median SI, 1.48 versus 2.13, P = 0.005), HLA-DQA1 (median SI, 1.75 versus 2.11, P = 0.007), and HLA-DQB1 (median SI, 1.48 versus 2.13, P = 0.002) loci, respectively.
5071 23649091 Similarly, we found that class I (HLA-A) and class II (HLA-DQA1 and HLA-DQB1) homozygosity was significantly associated with an overall decrease in LP compared with heterozygosity at those three loci.
5072 23649091 Specifically, individuals who were homozygous at these loci had significantly lower PA-specific LP than subjects heterozygous for HLA-A (median SI, 1.48 versus 2.13, P = 0.005), HLA-DQA1 (median SI, 1.75 versus 2.11, P = 0.007), and HLA-DQB1 (median SI, 1.48 versus 2.13, P = 0.002) loci, respectively.
5073 23658707 Analysis by immune outcome and stimulation status identified 27 genes (p≤0.0006 and FDR≤0.30) that responded differently to viral stimulation in high vs. low antibody responders, including major histocompatibility complex (MHC) class I genes (HLA-A, HLA-B and B2M with p = 0.0001, p = 0.0005 and p = 0.0002, respectively), and two genes related to innate immunity and inflammation (EMR3 and MEFV with p = 1.46E(-08) and p = 0.0004, respectively).
5074 23658773 A potential strategy is to induce CD8(+) and CD4(+) T cells that recognize epitopes within internal proteins that are less subject to antigenic drift.
5075 23658773 In vaccinated volunteers, the expression of Granzyme A, Perforin and CD57 on influenza HLA A*02 M158-66 antigen specific cells was higher than non-vaccinated volunteers before and after challenge despite a similar frequency of antigen specific cells.
5076 23704576 We found that simian immunodeficiency virus (SIV) protein-expressing rhesus cytomegalovirus (RhCMV) vectors elicit SIV-specific CD8(+) T cells that recognize unusual, diverse, and highly promiscuous epitopes, including dominant responses to epitopes restricted by class II major histocompatibility complex (MHC) molecules.
5077 23704576 Induction of canonical SIV epitope-specific CD8(+) T cell responses is suppressed by the RhCMV-encoded Rh189 gene (corresponding to human CMV US11), and the promiscuous MHC class I- and class II-restricted CD8(+) T cell responses occur only in the absence of the Rh157.5, Rh157.4, and Rh157.6 (human CMV UL128, UL130, and UL131) genes.
5078 23704576 We found that simian immunodeficiency virus (SIV) protein-expressing rhesus cytomegalovirus (RhCMV) vectors elicit SIV-specific CD8(+) T cells that recognize unusual, diverse, and highly promiscuous epitopes, including dominant responses to epitopes restricted by class II major histocompatibility complex (MHC) molecules.
5079 23704576 Induction of canonical SIV epitope-specific CD8(+) T cell responses is suppressed by the RhCMV-encoded Rh189 gene (corresponding to human CMV US11), and the promiscuous MHC class I- and class II-restricted CD8(+) T cell responses occur only in the absence of the Rh157.5, Rh157.4, and Rh157.6 (human CMV UL128, UL130, and UL131) genes.
5080 23716134 Egr2-knockdown (Egr2-KD) DCs showed increased levels of major histocompatability complex (MHC) class I and II and co-stimulatory molecules, and enhanced antigen uptake and migratory capacities.
5081 23716134 Furthermore, Egr2-KD abolished SOCS1 expression and signal transducer and activator of transcription 5 (STAT5) activation during DC development, probably resulting in the enhancement of IL-12 expression and Th1 immunogenicity of a DC vaccine.
5082 23717436 Treatment of whole tumor cells with ethanol resulted in blockade of immune-suppressive soluble factors such as transforming growth factor (TGF)-β1, vascular endothelial growth factor, and IL-10 without decreased expression of major histocompatibility complex (MHC) class I and the MUC1 tumor-associated antigen.
5083 23717436 Moreover, the ethanol-treated tumor cells expressed "eat-me" signals such as calreticulin (CRT) on the cell surface and released immunostimulatory factors such as heat shock protein (HSP)90α and high-mobility group box 1 (HMGB1).
5084 23729440 Consistent with their specific receptor expression, skin DCs bound and internalized Env via C-type lectin receptors, whereas blood DC subsets, including CD1c(+) myeloid DCs, CD123(+) plasmacytoid DCs (PDCs), and CD141(+) DCs exhibited a restricted repertoire of C-type lectin receptors and relied on CD4 for uptake of Env.
5085 23729440 Despite a generally poor capacity for Ag uptake compared with myeloid DCs, the high expression of CD4 on PDCs allowed them to bind and internalize Env very efficiently.
5086 23729440 CD4-mediated uptake delivered Env to EEA1(+) endosomes that progressed to Lamp1(+) and MHC class II(+) lysosomes where internalized Env was degraded rapidly.
5087 23732848 The vaccinated fish produced low while significant level of specific antibody and showed increased expression of immune-related factors including IL-1β, IFN-γ, MHC II, MHC-I and CD8, indicating that WED possesses significant immunoprotective potential.
5088 23738590 Identification of minimal human MHC-restricted CD8+ T-cell epitopes within the Plasmodium falciparum circumsporozoite protein (CSP).
5089 23745018 The results showed that consensus peptide identified SLAEKNITI had changes that indicated predicted escape mutation in strains of HIV responding to pressure exerted by CD8+ cells expressing HLA A*02.
5090 23745018 The predominating 9-mers IRIGPGQAF of gp120 are significantly less immunogenic toward HLA B*27 than to HLA A*02.
5091 23745018 The results showed that consensus peptide identified SLAEKNITI had changes that indicated predicted escape mutation in strains of HIV responding to pressure exerted by CD8+ cells expressing HLA A*02.
5092 23745018 The predominating 9-mers IRIGPGQAF of gp120 are significantly less immunogenic toward HLA B*27 than to HLA A*02.
5093 23757291 Subsequently, it was discovered that natural killer T cells recognized glycolipids when presented by the antigen presenting molecule CD1d.
5094 23771222 This resulted in a high-titer anti-α-syn antibody response on α-syn overexpression; the accumulation of CD4-positive, MHC II-positive ramified microglia in the substantia nigra; long-lasting infiltration of CD4-positive, Foxp3-positive cells throughout the nigrostriatal system; and fewer pathologic aggregates in the striatum versus control animals that had received a mock vaccine.
5095 23774693 We demonstrated that LD1ED III possesses an inherent immunostimulation ability that can activate RAW 264.7 macrophage cells by up-regulating their expression of CD40, CD80, CD83, CD86 and MHC II, whereas D1ED III could not induce the up-regulation of these molecules.
5096 23776170 HLA-A*01:03, HLA-A*24:02, HLA-B*08:01, HLA-B*27:05, HLA-B*35:01, HLA-B*44:02, and HLA-C*07:01 monochain transgenic/H-2 class I null mice: novel versatile preclinical models of human T cell responses.
5097 23776170 In combination with the previously created HLA-A*02:01 and -B*07:02 transgenic mice, the novel HLA transgenic mice described in this report should be a versatile preclinical animal model that will speed up the identification and optimization of HLA-restricted CD8(+) T cell epitopes of potential interest in various autoimmune human diseases and in preclinical evaluation of T cell-based vaccines.
5098 23776170 HLA-A*01:03, HLA-A*24:02, HLA-B*08:01, HLA-B*27:05, HLA-B*35:01, HLA-B*44:02, and HLA-C*07:01 monochain transgenic/H-2 class I null mice: novel versatile preclinical models of human T cell responses.
5099 23776170 In combination with the previously created HLA-A*02:01 and -B*07:02 transgenic mice, the novel HLA transgenic mice described in this report should be a versatile preclinical animal model that will speed up the identification and optimization of HLA-restricted CD8(+) T cell epitopes of potential interest in various autoimmune human diseases and in preclinical evaluation of T cell-based vaccines.
5100 23825389 DCs treated with RpfB displayed features of mature and functional status, with elevated expression of cell surface molecules (CD80, CD86, and MHC class I and II) and proinflammatory cytokine production (TNF-α, IL-1β, IL-6, and IL-12p70).
5101 23825389 RpfB-treated DCs effectively polarized naïve CD4(+) and CD8(+) T cells to secrete IFN-γ and IL-2.
5102 23825389 Importantly, RpfB induced the expansion of memory CD4(+)/CD8(+)CD44(high)CD62L(low) T cells in the spleen of M. tuberculosis-infected mice.
5103 23825678 Bee Venom Phospholipase A2, a Good "Chauffeur" for Delivering Tumor Antigen to the MHC I and MHC II Peptide-Loading Compartments of the Dendritic Cells: The Case of NY-ESO-1.
5104 23825678 To confirm this feature, in this study the fusion protein PNY, composed of NY-ESO-1(NY(s)) fused to the C-terminus of bvPLA2m, was engineered. bvPLA2m enhanced the binding of NY(s) to the membrane of human monocyte-derived dendritic cells (DCs) and, once taken up by the cells, the antigen fused to the vector was directed to both MHC I and MHC II peptide-loading compartments. bvPLA2m was shown to increase the cross-presentation of the NY(s)-derived, restricted HLA-A*02 peptide, NY-ESO-1157-165(NY157-165), at the T1 cell surface.
5105 23825678 Of these CD8+ T-cell lines, two were able to recognize the human melanoma cell line, SK-MEL-37, in a context of HLA-A*02.
5106 23825678 Bee Venom Phospholipase A2, a Good "Chauffeur" for Delivering Tumor Antigen to the MHC I and MHC II Peptide-Loading Compartments of the Dendritic Cells: The Case of NY-ESO-1.
5107 23825678 To confirm this feature, in this study the fusion protein PNY, composed of NY-ESO-1(NY(s)) fused to the C-terminus of bvPLA2m, was engineered. bvPLA2m enhanced the binding of NY(s) to the membrane of human monocyte-derived dendritic cells (DCs) and, once taken up by the cells, the antigen fused to the vector was directed to both MHC I and MHC II peptide-loading compartments. bvPLA2m was shown to increase the cross-presentation of the NY(s)-derived, restricted HLA-A*02 peptide, NY-ESO-1157-165(NY157-165), at the T1 cell surface.
5108 23825678 Of these CD8+ T-cell lines, two were able to recognize the human melanoma cell line, SK-MEL-37, in a context of HLA-A*02.
5109 23825678 Bee Venom Phospholipase A2, a Good "Chauffeur" for Delivering Tumor Antigen to the MHC I and MHC II Peptide-Loading Compartments of the Dendritic Cells: The Case of NY-ESO-1.
5110 23825678 To confirm this feature, in this study the fusion protein PNY, composed of NY-ESO-1(NY(s)) fused to the C-terminus of bvPLA2m, was engineered. bvPLA2m enhanced the binding of NY(s) to the membrane of human monocyte-derived dendritic cells (DCs) and, once taken up by the cells, the antigen fused to the vector was directed to both MHC I and MHC II peptide-loading compartments. bvPLA2m was shown to increase the cross-presentation of the NY(s)-derived, restricted HLA-A*02 peptide, NY-ESO-1157-165(NY157-165), at the T1 cell surface.
5111 23825678 Of these CD8+ T-cell lines, two were able to recognize the human melanoma cell line, SK-MEL-37, in a context of HLA-A*02.
5112 23840706 Delivery of LmSTI1a to adjuvant-matured DCs increased the frequency of antigen-specific CD4(+) T cells producing IFN-γ(+), IL-2(+), and TNF-α(+) in two different strains of mice (C57BL/6 and Balb/c), while such responses were not observed with the same doses of a control Ig-LmSTI1a mAb without receptor affinity or with non-targeted LmSTI1a protein.
5113 23840706 Using a peptide library for LmSTI1a, we identified at least two distinct CD4(+) T cell mimetopes in each MHC class II haplotype, consistent with the induction of broad immunity.
5114 23840706 When we compared T cell immune responses generated after targeting DCs with LmSTI1a or other L. major antigens, including LACK (Leishmania receptor for activated C kinase) and LeIF (Leishmania eukaryotic ribosomal elongation and initiation factor 4a), we found that LmSTI1a was superior for generation of IFN-γ-producing CD4(+) T cells, which correlated with higher protection of susceptible Balb/c mice to a challenge with L. major.
5115 23847615 Re-Directing CD4(+) T Cell Responses with the Flanking Residues of MHC Class II-Bound Peptides: The Core is Not Enough.
5116 23847615 There are two main subsets of αβ T cells: CD8(+) T cells that recognize mainly cytosol-derived peptides in the context of MHC class I (pMHC-I), and CD4(+) T cells that recognize peptides usually derived from exogenous proteins presented by MHC class II (pMHC-II).
5117 23847615 Although pMHC-I and pMHC-II play a virtually identical role during T cell responses (T cell antigen presentation) and are very similar in overall conformation, there exist a number of subtle but important differences that may govern the functional dichotomy observed between CD8(+) and CD4(+) T cells.
5118 23847615 Re-Directing CD4(+) T Cell Responses with the Flanking Residues of MHC Class II-Bound Peptides: The Core is Not Enough.
5119 23847615 There are two main subsets of αβ T cells: CD8(+) T cells that recognize mainly cytosol-derived peptides in the context of MHC class I (pMHC-I), and CD4(+) T cells that recognize peptides usually derived from exogenous proteins presented by MHC class II (pMHC-II).
5120 23847615 Although pMHC-I and pMHC-II play a virtually identical role during T cell responses (T cell antigen presentation) and are very similar in overall conformation, there exist a number of subtle but important differences that may govern the functional dichotomy observed between CD8(+) and CD4(+) T cells.
5121 23898209 Mucosa-associated invariant T (MAIT) cells are "innate" T cells that express an invariant T-cell receptor α-chain restricted by the nonclassical MHC class I molecule MHC-related protein 1 (MR1).
5122 23898209 Mechanistic studies showed that MAIT cells required both MR1 and IL-12 40 kDa subunit (IL-12p40) signals from infected antigen presenting cells to control F. tularensis LVS intracellular growth.
5123 23898209 Importantly, pulmonary F. tularensis LVS infection of MR1-deficient (MR1(-/-)) mice, which lack MAIT cells, revealed defects in early mucosal cytokine production, timely recruitment of IFN-γ-producing CD4(+) and CD8(+) T cells to the infected lungs, and control of pulmonary F. tularensis LVS growth.
5124 23900783 NetMHCIIpan-3.0, a common pan-specific MHC class II prediction method including all three human MHC class II isotypes, HLA-DR, HLA-DP and HLA-DQ.
5125 23900783 The method employs a strategy common for HLA-DR, HLA-DP and HLA-DQ molecules to define the peptide-binding MHC environment in terms of a pseudo sequence.
5126 23900783 NetMHCIIpan-3.0, a common pan-specific MHC class II prediction method including all three human MHC class II isotypes, HLA-DR, HLA-DP and HLA-DQ.
5127 23900783 The method employs a strategy common for HLA-DR, HLA-DP and HLA-DQ molecules to define the peptide-binding MHC environment in terms of a pseudo sequence.
5128 23903757 In this study, we established GPC3‑derived peptide-specific CTL clones from the PBMCs of an HLA-A*02:07-positive patient with HCC who was vaccinated with an HLA-A2-restricted GPC3 peptide vaccine and showed a clinical response in the phase I clinical trial.
5129 23904160 We hypothesized that CD4(+) and CD8(+) T cell responses with a heterologous prime/boost vaccine approach could induce long-lived vaccine efficacy against M. tuberculosis in C57BL/6 mice.
5130 23904160 We produced an adenovirus vector expressing ID93 (Ad5-ID93) for induction of CD8 T cells to use with our candidate tuberculosis vaccine, ID93/glucopyranosyl lipid adjuvant (GLA)-stable emulsion (SE), which induces potent Th1 CD4 T cells.
5131 23904160 When Ad5-ID93 is administered in a prime-boost strategy with ID93/GLA-SE, both CD4(+) and CD8(+) T cells are generated and provide protection against M. tuberculosis.
5132 23904160 In a MHC class I-deficient mouse model, all groups including the Ad5-ID93 group elicited an Ag-specific CD4(+) T cell response and significantly fewer Ag-specific CD8(+) T cells, but were still protected against M. tuberculosis, suggesting that CD4(+) Th1 T cells could compensate for the loss of CD8(+) T cells.
5133 23904160 One of the correlates of protection between these two approaches was an increase in the total number of ID93-specific IFN-γ-producing CD4(+) T cells 6 mo following the last immunization.
5134 23908656 Analysis, Isolation, and Activation of Antigen-Specific CD4(+) and CD8(+) T Cells by Soluble MHC-Peptide Complexes.
5135 23908656 This is possible by means of soluble recombinant ligands for T cells, i.e., MHC class I-peptide (pMHC I) complexes for CD8(+) T cells and MHC class II-peptide (pMHC II) complexes for CD4(+) T cells and flow cytometry.
5136 23908656 Analysis, Isolation, and Activation of Antigen-Specific CD4(+) and CD8(+) T Cells by Soluble MHC-Peptide Complexes.
5137 23908656 This is possible by means of soluble recombinant ligands for T cells, i.e., MHC class I-peptide (pMHC I) complexes for CD8(+) T cells and MHC class II-peptide (pMHC II) complexes for CD4(+) T cells and flow cytometry.
5138 23911739 Pneumococcal, HLA class I and II and major histocompatibility class I-related chain A (MICA) antibodies were determined by Luminex™ technology (xMAP™ Pneumococcal Immunity Panel and LABScreen™ Mixed beads, respectively) and HLA antibodies also by ELISA (Lambda Antigen Tray™).
5139 23911739 Positive Luminex™ reactions were present in 63%, 67% and 63% (HLA class I), 47%, 47% and 55% (HLA class II) and 29%, 29% and 29% (MICA) pre-vaccination, at month 1 and 15, respectively.
5140 23911739 Pneumococcal, HLA class I and II and major histocompatibility class I-related chain A (MICA) antibodies were determined by Luminex™ technology (xMAP™ Pneumococcal Immunity Panel and LABScreen™ Mixed beads, respectively) and HLA antibodies also by ELISA (Lambda Antigen Tray™).
5141 23911739 Positive Luminex™ reactions were present in 63%, 67% and 63% (HLA class I), 47%, 47% and 55% (HLA class II) and 29%, 29% and 29% (MICA) pre-vaccination, at month 1 and 15, respectively.
5142 23922366 Here we explore the association between killer cell immunoglobulin-like receptor (KIR)/HLA and human immunodeficiency virus type 1 (HIV-1) acquisition with different viral subtypes circulating in East Africa.
5143 23922366 In the prospective Cohort Development (CODE) cohort (Mbeya, Tanzania), carriers of KIR3DS1 and its putative ligand (HLA-A or HLA-B Bw4-80Ile alleles) showed increased HIV-1 acquisition risk (odds ratio [OR] = 3.46; 95% confidence interval [CI], 1.12-10.63; P = .04) and a trend for enrichment for subtype A and A-containing recombinants (78% vs. 46%; OR = 4.05; 95% CI, .91-28.30; P = .09) at the expense of subtype C (11% vs. 43%; OR = 0.17; 95% CI, .01-.97; P = .08).
5144 23997182 An immunodominant HLA-A*1101-restricted CD8+ T-cell response targeting hepatitis B surface antigen in chronic hepatitis B patients.
5145 23997182 Here, we describe an immunodominant CD8(+) T-cell response targeting a hepatitis B surface antigen determinant (HBs(295-304)) restricted by HLA-A*1101 in both healthy individuals and CHB patients.
5146 23997182 An immunodominant HLA-A*1101-restricted CD8+ T-cell response targeting hepatitis B surface antigen in chronic hepatitis B patients.
5147 23997182 Here, we describe an immunodominant CD8(+) T-cell response targeting a hepatitis B surface antigen determinant (HBs(295-304)) restricted by HLA-A*1101 in both healthy individuals and CHB patients.
5148 24012585 However, homozygosity at HLA-A, HLA-B or HLA-C conferred no observable disadvantage in our study population (P = 0.730, 0.246 and 0.445, respectively).
5149 24032635 Here we identified novel human leucocyte antigen (HLA)-A*0201 (HLA-A2)-restricted cytotoxic T lymphocyte (CTL) epitopes from a B cell specific molecule HLA-DOβ (DOB) as a potential target for MM.
5150 24053400 The cytotoxic CD8(+) T lymphocyte-mediated cellular response is important for the elimination of virus-infected cells and requires the prior recognition of short viral peptide antigens previously translocated to the endoplasmic reticulum by the transporter associated with antigen processing (TAP).
5151 24053400 However, individuals with nonfunctional TAP complexes or infected cells with TAP molecules blocked by specific viral proteins, such as the cowpoxvirus, a component of the first source of early empirical vaccination against smallpox, are still able to present several HLA class I ligands generated by the TAP-independent antigen processing pathways to specific cytotoxic CD8(+) T lymphocytes.
5152 24075919 These SNPs were found to regulate the expression of a group of genes involved in antigen processing and presentation including HLA-A, HLA-C, HLA-G, HLA-H, HLA-DRA, HLA-DRB1, HLA-DRB5, HLA-DQA1, HLA-DQB1, HLA-DOB, and TAP-2.
5153 24086507 Control of parasite replication exerted by MHC class I restricted CD8+ T-cells in the liver is critical for vaccination-induced protection against malaria.
5154 24086507 Furthermore, infected cells showed no obvious defects in their capacity to upregulate expression of different molecular components of the MHC class I machinery in response to pro-inflammatory lymphokines or trigger direct activation of allo-specific or peptide-specific human CD8+ T-cells.
5155 24086507 Control of parasite replication exerted by MHC class I restricted CD8+ T-cells in the liver is critical for vaccination-induced protection against malaria.
5156 24086507 Furthermore, infected cells showed no obvious defects in their capacity to upregulate expression of different molecular components of the MHC class I machinery in response to pro-inflammatory lymphokines or trigger direct activation of allo-specific or peptide-specific human CD8+ T-cells.
5157 24095953 We have shown that IFN-α 1) up-regulates the expression of MHC II, CD40, CD83, CD80 and CD86 molecules on BMDCs; 2) down-regulates the rates of pinocytosis and phagocytosis by BMDCs as evidenced by the results of decreased ACP, and FITC-dextran bio-assay; 3) enhances the ability of BMDCs to drive T cell function; and 4) induces higher levels of IL-12 and TNF-α secreted by BMDCs.
5158 24099705 Exposing SiO2@LDH nanoparticles to macrophages caused a higher dose-dependent expression of IFN-γ, IL-6, CD86 and MHC II, compared with SiO2 and LDH respectively.
5159 24101547 Asymptomatic HLA-A*02:01-restricted epitopes from herpes simplex virus glycoprotein B preferentially recall polyfunctional CD8+ T cells from seropositive asymptomatic individuals and protect HLA transgenic mice against ocular herpes.
5160 24101547 In this study, we used multiple prediction algorithms to identify 10 potential HLA-A*02:01-restricted CD8(+) T cell epitopes from the HSV-1 gB amino acid sequence.
5161 24101547 In 10 sequentially studied HLA-A*02:01-positive, HSV-1-seropositive ASYMP individuals, the most frequent, robust, and polyfunctional CD8(+) T cell responses, as assessed by a combination of tetramer, IFN-γ-ELISPOT, CFSE proliferation, CD107a/b cytotoxic degranulation, and multiplex cytokine assays, were directed mainly against epitopes gB342-350 and gB561-569.
5162 24101547 In contrast, in 10 HLA-A*02:01-positive, HSV-1-seropositive symptomatic (SYMP) individuals (with a history of numerous episodes of recurrent clinical herpes disease) frequent, but less robust, CD8(+) T cell responses were directed mainly against nonoverlapping epitopes (gB183-191 and gB441-449).
5163 24101547 ASYMP individuals had a significantly higher proportion of HSV-gB-specific CD8(+) T cells expressing CD107a/b degranulation marker and producing effector cytokines IL-2, IFN-γ, and TNF-α than did SYMP individuals.
5164 24101547 Moreover, immunization of a novel herpes-susceptible HLA-A*02:01 transgenic mouse model with ASYMP epitopes, but not with SYMP epitopes, induced strong CD8(+) T cell-dependent protective immunity against ocular herpes infection and disease.
5165 24101547 Asymptomatic HLA-A*02:01-restricted epitopes from herpes simplex virus glycoprotein B preferentially recall polyfunctional CD8+ T cells from seropositive asymptomatic individuals and protect HLA transgenic mice against ocular herpes.
5166 24101547 In this study, we used multiple prediction algorithms to identify 10 potential HLA-A*02:01-restricted CD8(+) T cell epitopes from the HSV-1 gB amino acid sequence.
5167 24101547 In 10 sequentially studied HLA-A*02:01-positive, HSV-1-seropositive ASYMP individuals, the most frequent, robust, and polyfunctional CD8(+) T cell responses, as assessed by a combination of tetramer, IFN-γ-ELISPOT, CFSE proliferation, CD107a/b cytotoxic degranulation, and multiplex cytokine assays, were directed mainly against epitopes gB342-350 and gB561-569.
5168 24101547 In contrast, in 10 HLA-A*02:01-positive, HSV-1-seropositive symptomatic (SYMP) individuals (with a history of numerous episodes of recurrent clinical herpes disease) frequent, but less robust, CD8(+) T cell responses were directed mainly against nonoverlapping epitopes (gB183-191 and gB441-449).
5169 24101547 ASYMP individuals had a significantly higher proportion of HSV-gB-specific CD8(+) T cells expressing CD107a/b degranulation marker and producing effector cytokines IL-2, IFN-γ, and TNF-α than did SYMP individuals.
5170 24101547 Moreover, immunization of a novel herpes-susceptible HLA-A*02:01 transgenic mouse model with ASYMP epitopes, but not with SYMP epitopes, induced strong CD8(+) T cell-dependent protective immunity against ocular herpes infection and disease.
5171 24101547 Asymptomatic HLA-A*02:01-restricted epitopes from herpes simplex virus glycoprotein B preferentially recall polyfunctional CD8+ T cells from seropositive asymptomatic individuals and protect HLA transgenic mice against ocular herpes.
5172 24101547 In this study, we used multiple prediction algorithms to identify 10 potential HLA-A*02:01-restricted CD8(+) T cell epitopes from the HSV-1 gB amino acid sequence.
5173 24101547 In 10 sequentially studied HLA-A*02:01-positive, HSV-1-seropositive ASYMP individuals, the most frequent, robust, and polyfunctional CD8(+) T cell responses, as assessed by a combination of tetramer, IFN-γ-ELISPOT, CFSE proliferation, CD107a/b cytotoxic degranulation, and multiplex cytokine assays, were directed mainly against epitopes gB342-350 and gB561-569.
5174 24101547 In contrast, in 10 HLA-A*02:01-positive, HSV-1-seropositive symptomatic (SYMP) individuals (with a history of numerous episodes of recurrent clinical herpes disease) frequent, but less robust, CD8(+) T cell responses were directed mainly against nonoverlapping epitopes (gB183-191 and gB441-449).
5175 24101547 ASYMP individuals had a significantly higher proportion of HSV-gB-specific CD8(+) T cells expressing CD107a/b degranulation marker and producing effector cytokines IL-2, IFN-γ, and TNF-α than did SYMP individuals.
5176 24101547 Moreover, immunization of a novel herpes-susceptible HLA-A*02:01 transgenic mouse model with ASYMP epitopes, but not with SYMP epitopes, induced strong CD8(+) T cell-dependent protective immunity against ocular herpes infection and disease.
5177 24101547 Asymptomatic HLA-A*02:01-restricted epitopes from herpes simplex virus glycoprotein B preferentially recall polyfunctional CD8+ T cells from seropositive asymptomatic individuals and protect HLA transgenic mice against ocular herpes.
5178 24101547 In this study, we used multiple prediction algorithms to identify 10 potential HLA-A*02:01-restricted CD8(+) T cell epitopes from the HSV-1 gB amino acid sequence.
5179 24101547 In 10 sequentially studied HLA-A*02:01-positive, HSV-1-seropositive ASYMP individuals, the most frequent, robust, and polyfunctional CD8(+) T cell responses, as assessed by a combination of tetramer, IFN-γ-ELISPOT, CFSE proliferation, CD107a/b cytotoxic degranulation, and multiplex cytokine assays, were directed mainly against epitopes gB342-350 and gB561-569.
5180 24101547 In contrast, in 10 HLA-A*02:01-positive, HSV-1-seropositive symptomatic (SYMP) individuals (with a history of numerous episodes of recurrent clinical herpes disease) frequent, but less robust, CD8(+) T cell responses were directed mainly against nonoverlapping epitopes (gB183-191 and gB441-449).
5181 24101547 ASYMP individuals had a significantly higher proportion of HSV-gB-specific CD8(+) T cells expressing CD107a/b degranulation marker and producing effector cytokines IL-2, IFN-γ, and TNF-α than did SYMP individuals.
5182 24101547 Moreover, immunization of a novel herpes-susceptible HLA-A*02:01 transgenic mouse model with ASYMP epitopes, but not with SYMP epitopes, induced strong CD8(+) T cell-dependent protective immunity against ocular herpes infection and disease.
5183 24101547 Asymptomatic HLA-A*02:01-restricted epitopes from herpes simplex virus glycoprotein B preferentially recall polyfunctional CD8+ T cells from seropositive asymptomatic individuals and protect HLA transgenic mice against ocular herpes.
5184 24101547 In this study, we used multiple prediction algorithms to identify 10 potential HLA-A*02:01-restricted CD8(+) T cell epitopes from the HSV-1 gB amino acid sequence.
5185 24101547 In 10 sequentially studied HLA-A*02:01-positive, HSV-1-seropositive ASYMP individuals, the most frequent, robust, and polyfunctional CD8(+) T cell responses, as assessed by a combination of tetramer, IFN-γ-ELISPOT, CFSE proliferation, CD107a/b cytotoxic degranulation, and multiplex cytokine assays, were directed mainly against epitopes gB342-350 and gB561-569.
5186 24101547 In contrast, in 10 HLA-A*02:01-positive, HSV-1-seropositive symptomatic (SYMP) individuals (with a history of numerous episodes of recurrent clinical herpes disease) frequent, but less robust, CD8(+) T cell responses were directed mainly against nonoverlapping epitopes (gB183-191 and gB441-449).
5187 24101547 ASYMP individuals had a significantly higher proportion of HSV-gB-specific CD8(+) T cells expressing CD107a/b degranulation marker and producing effector cytokines IL-2, IFN-γ, and TNF-α than did SYMP individuals.
5188 24101547 Moreover, immunization of a novel herpes-susceptible HLA-A*02:01 transgenic mouse model with ASYMP epitopes, but not with SYMP epitopes, induced strong CD8(+) T cell-dependent protective immunity against ocular herpes infection and disease.
5189 24108701 Altered peptide ligands (APLs) were designed to enhance MHC binding and hence T cell recognition of gp100 in HLA-DR4(+) melanoma patients.
5190 24108701 Nevertheless, heterogeneous preferences of CD4(+) T cells from several HLA-DR4(+) melanoma patients for different gp100 APLs suggested highly variable TCR usage, even among six patients who had been vaccinated against the wild-type gp100 peptide.
5191 24109221 We measured ADCC responses in plasma to a panel of H1 and H3 hemagglutinin (HA) proteins and influenza virus-specific CD8 T cell (CTL) responses using a sensitive major histocompatibility complex (MHC) tetramer reagent.
5192 24123688 Both particles decreased frequencies of stimulatory CD11b(+)MHC class II(hi) allergen-laden DC in the draining LN, with PS50G having the more pronounced effect.
5193 24130485 This recognition depends on the detection of microbial compounds presented by the evolutionarily conserved major-histocompatibility-complex (MHC) class I molecule, MR1.
5194 24130485 The NK receptor, CD161, highly expressed by MAIT cells, modulated the cytokine but not the cytotoxic response triggered by bacteria infected cells.
5195 24130917 In order to expand our knowledge of HLA-restricted dengue epitopes, we screened T-cell responses against 477 overlapping peptides derived from structural and non-structural proteins of the dengue virus serotype 3 (DENV3) by use of HLA class I and II transgenic mice (TgM): A2, A24, B7, DR2, DR3 and DR4.
5196 24138415 By using molecular docking and molecular dynamics simulation, we examine the influence of His protonation/deprotonation on peptide binding affinity to MHC class II proteins from locus HLA-DP.
5197 24144535 The method was part of the 2nd Machine Learning Competition in Immunology and yielded state-of-the-art accuracy for the prediction of peptides eluted from human HLA-A*02:01, HLA-B*07:02, HLA-B*35:01, HLA-B*44:03, HLA-B*53:01, HLA-B*57:01 and mouse H2-D(b) and H2-K(b) MHC molecules.
5198 24166949 Cooperation between CD4 T cells and B cells to produce antibodies is thought to be critical for clearance of Py17XNL parasites from the blood, with major histocompatibility complex (MHC) class II molecules being required for activation of CD4 T cells.
5199 24166949 In a series of experiments, we determined that the inability of humanized DR0401.EA(0) mice to elicit specific antibodies was due to expansion and activation of regulatory CD4(+) Foxp3(+) T cells (Tregs) that suppressed B cells to secrete antibodies through cell-cell interactions.
5200 24167504 Other peptides within the antigen that can bind to host MHC molecules and recruit CD4 T cells as single peptides are termed "cryptic" because they fail to induce responses when expressed in complex proteins or when in competition with other peptides during the immune response.
5201 24167504 In the last decade, our laboratory has evaluated the mechanisms that underlie the preferential specificity of CD4 T cells and have discovered that both intracellular events within antigen presenting cells, particular selective DM editing, and intercellular regulatory pathways, involving IFN-γ, indoleamine 2,3-dioxygenase, and regulatory T cells, play a role in selecting the final peptide specificity of CD4 T cells.
5202 24190657 Although no stringent correlate was defined, on average HLA B alleles are associated with significantly narrower repertoires than are HLA A alleles.
5203 24244595 We demonstrate that targeting to MHC class II molecules predominantly induced an antibody/Th2 response, whereas targeting to CCR1/3/5 predominantly induced a CD8(+)/Th1 T cell response.
5204 24248811 Association and differentiation of MHC class I and II polymorphic Alu insertions and HLA-A, -B, -C and -DRB1 alleles in the Chinese Han population.
5205 24248811 In order to investigate the polymorphism of Alu insertions (POALINs) in the HLA region, we genotyped ten Alu loci (AluMICB, AluTF, AluHJ, AluHG, AluHF in the HLA class I region and AluDPB2, AluDQA2, AluDQA1, AluDRB1, AluORF10 in the HLA class II region) to determine their allele frequencies and associations with the HLA-A, HLA-B, HLA-C and HLA-DRB1 genes in the Chinese Han population.
5206 24248811 Each POALIN was in significant linkage disequilibrium with a variety of HLA-A, -B, -C and -DRB1 alleles, and was associated with a variety of HLA-A, -B, -C and -DRB1 allele in Chinese Han.
5207 24248811 Association and differentiation of MHC class I and II polymorphic Alu insertions and HLA-A, -B, -C and -DRB1 alleles in the Chinese Han population.
5208 24248811 In order to investigate the polymorphism of Alu insertions (POALINs) in the HLA region, we genotyped ten Alu loci (AluMICB, AluTF, AluHJ, AluHG, AluHF in the HLA class I region and AluDPB2, AluDQA2, AluDQA1, AluDRB1, AluORF10 in the HLA class II region) to determine their allele frequencies and associations with the HLA-A, HLA-B, HLA-C and HLA-DRB1 genes in the Chinese Han population.
5209 24248811 Each POALIN was in significant linkage disequilibrium with a variety of HLA-A, -B, -C and -DRB1 alleles, and was associated with a variety of HLA-A, -B, -C and -DRB1 allele in Chinese Han.
5210 24248811 Association and differentiation of MHC class I and II polymorphic Alu insertions and HLA-A, -B, -C and -DRB1 alleles in the Chinese Han population.
5211 24248811 In order to investigate the polymorphism of Alu insertions (POALINs) in the HLA region, we genotyped ten Alu loci (AluMICB, AluTF, AluHJ, AluHG, AluHF in the HLA class I region and AluDPB2, AluDQA2, AluDQA1, AluDRB1, AluORF10 in the HLA class II region) to determine their allele frequencies and associations with the HLA-A, HLA-B, HLA-C and HLA-DRB1 genes in the Chinese Han population.
5212 24248811 Each POALIN was in significant linkage disequilibrium with a variety of HLA-A, -B, -C and -DRB1 alleles, and was associated with a variety of HLA-A, -B, -C and -DRB1 allele in Chinese Han.
5213 24252697 In vitro, PS-F2 stimulated dendritic cells (DCs) to produce proinflammatory cytokines, including TNF-α, interleukin (IL)-6, and IL-12/IL-23 p40.
5214 24252697 PS-F2 also stimulated DCs to express the maturation markers CD40, CD80, CD86, and MHC class II.
5215 24252697 In a murine splenocyte culture, PS-F2 treatment resulted in elevated expression of T-bet and interferon (IFN)-γ in T lymphocytes.
5216 24275080 We have applied immunoinformatics techniques based on principal component analysis to evaluate patterns in predicted B-cell linear epitopes, MHC binding affinity and cathepsin cleavage in the hemagglutinin neuraminidase protein of vaccine strains and wild-type mumps isolates.
5217 24275080 We have mapped predicted MHC-peptide binding for 37 MHC-I and 28 MHC-II alleles and predicted cleavage by cathepsin B, L and S.
5218 24275080 We have applied immunoinformatics techniques based on principal component analysis to evaluate patterns in predicted B-cell linear epitopes, MHC binding affinity and cathepsin cleavage in the hemagglutinin neuraminidase protein of vaccine strains and wild-type mumps isolates.
5219 24275080 We have mapped predicted MHC-peptide binding for 37 MHC-I and 28 MHC-II alleles and predicted cleavage by cathepsin B, L and S.
5220 24327810 In the present study, we show that culture fluids from both PAI-stimulated peripheral blood mononuclear cells (PBMC) and CD8+ T-cells of HIV-1 infected patients were able to suppress HIV-1 replication in an MHC-unrestricted fashion.
5221 24327810 The PAI-induced antiviral activity was eliminated when culture fluids were pre-heated at 100°C for 10 min. and it is associated with induction of IFN-γ, MIP-1α, MIP-1β, and RANTES production, but inhibition of IL-10.
5222 24327810 Furthermore, this induction is dependent on the immunological status (CD4:CD8 ratio) of the HIV-1 infected patient.
5223 24362891 T cells autoreactive to the antigen-presenting molecule CD1a are common in human blood and skin, but the search for natural autoantigens has been confounded by background T cell responses to CD1 proteins and self lipids.
5224 24387268 IGRP and insulin vaccination induce CD8+ T cell-mediated autoimmune diabetes in the RIP-CD80GP mouse.
5225 24387268 Of 14 pancreatic proteins tested by DNA vaccination, murine pre-proinsulin 2 (100% of mice; median time after vaccination, 60 days) and islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) (77%, 58 days) could induce diabetes.
5226 24387268 Vaccination with DNA encoding for zinc transporter 8, Ia-2, Ia-2β, glutamic acid decarboxylase 67 (Gad67), chromogranin A, insulinoma amyloid polypeptide and homeobox protein Nkx-2.2 induced diabetes development in 25-33% of mice.
5227 24387268 Vaccination with DNA encoding for Gad65, secretogranin 5, pancreas/duodenum homeobox protein 1 (Pdx1), carboxyl ester lipase, glucagon and control hepatitis B surface antigen (HBsAg) induced diabetes in <20% of mice.
5228 24387268 CD8(+) T cell targets of IGRP were identified with a peptide library-based enzyme-linked immunospot assay, and diabetes could also be induced by vaccination with major histocompatibility complex (MHC) class I-restricted IGRP peptides loaded on mature dendritic cells.
5229 24415578 Therefore, we analyzed a cohort of patients with a primary (n = 43) and subsequent recurrent uVIN lesion (n = 20), vaccine-treated uVIN patients (n = 12), patients with human papillomavirus (HPV)-induced vulvar carcinoma (n = 21) and healthy controls (n = 26) for the expression of classical HLA-class I/II and nonclassical HLA-E/-G and MHC class I chain-related molecule A (MICA).
5230 24415578 Of the nonclassical molecules, MICA was downregulated in 80% of uVIN whereas HLA-E and -G were expressed in a minority of cases.
5231 24422723 In six patients, WT1-specific CTL responses were detected using enzyme-linked immunosorbent spot assays and pWT126/HLA-A*0201 tetramer staining, after ex vivo stimulation with the relevant WT1 peptides.
5232 24422723 However, re-stimulation of these WT1-specific T cells failed to elicit secondary expansion in all four patients tested, suggesting that the WT1-specific CD8(+) T cells generated following vaccination may be functionally impaired.
5233 24426287 Among the genes studied, IFN α, IFN γ, MHC I and DDX 1 were up-regulated while IL 6 was down regulated.
5234 24455776 We have found that LDN enhances maturation of BMDCs as evidenced by 1) up-regulating the expression of MHC II, CD40, CD83, CD80 and CD86 molecules on BMDCs; 2) down-regulating the rates of pinocytosis and phagocytosis accompanied by the results of decreased ACP, and FITC-dextran bio-assay; 3) mounting potential of BMDCs to drive T cell; and 4) inducing secretion of higher levels of IL-12 and TNF-α.
5235 24475163 Human leukocyte antigen (HLA) class I molecules are critical components of the cell-mediated immune system that bind and present intracellular antigenic peptides to CD8(+) T cell receptors.
5236 24475289 Spores promoted activation of antigen presenting cells as demonstrated by the upregulation of MHC and CD40 molecules and enhanced secretion of pro-inflammatory cytokines by murine dendritic cells.
5237 24475289 In addition, in vivo studies indicated a direct role of the innate immunity on the immunomodulatory properties of B. subtilis spores, as demonstrated by the lack of adjuvant effects on MyD88 and TLR2 knockout mouse strains.
5238 24498044 In the present study, 131 candidate peptides were selected from the major immunodominant proteins (MIPs) of C. burnetii due to their high-affinity binding capacity for the MHC class II molecule H2 I-A(b) based on bioinformatic analyses.
5239 24498044 Twenty-two of the candidate peptides with distinct MIP epitopes were well recognized by the IFN-γ recall responses of CD4(+) T cells from mice immunized with parental proteins in an ELISPOT assay.
5240 24498547 Here, we report the results of a Phase I clinical trial to investigate the safety, immunostimulatory effects, and antineoplastic activity of a multi-target vaccine composed of four distinct peptides derived from cancer-testis (CT) antigens and vascular endothelial growth factor receptors (VEGFRs).
5241 24498547 Each patient was vaccinated with HLA-A*2402-restricted peptides derived from the CT antigens kinesin family member 20A (KIF20A) and cell division cycle-associated 1 (CDCA1) as well as from VEGFR1 and VEGFR2 subcutaneously once a week, and disease progression was evaluated up to 6 mo later.
5242 24509173 Patients received HLA-A*24:02-restricted, modified 9-mer WT1 peptide (3 mg/body) emulsified with Montanide ISA51 adjuvant (WT1 vaccine) intradermally biweekly and gemcitabine (1000 mg/m) on days 1, 8, and 15 of a 28-day cycle.
5243 24515851 These results bring a new perspective on the crosstalk between the MHC class II and MHC class I antigen-processing pathways, and may inspire new ideas for the design of vaccines against viruses and tumors.
5244 24599530 Here, we elucidate for the first time the dominant major histocompatibility complex (MHC) class II-presented B. pertussis CD4(+) T cell epitopes, expressed on human monocyte-derived dendritic cells (MDDC) after the processing of whole bacterial cells by use of a platform of immunoproteomics technology.
5245 24599530 Pertussis epitopes identified in the context of HLA-DR molecules were derived from two envelope proteins, i.e., putative periplasmic protein (PPP) and putative peptidoglycan-associated lipoprotein (PAL), and from two cytosolic proteins, i.e., 10-kDa chaperonin groES protein (groES) and adenylosuccinate synthetase (ASS).
5246 24599530 CD4(+) T cell responsiveness in healthy adults against peptide pools representing epitope regions or full proteins confirmed the immunogenicity of PAL, PPP, groES, and ASS.
5247 24599530 Elevated lymphoproliferative activity to PPP, groES, and ASS in subjects within a year after the diagnosis of symptomatic pertussis suggested immunogenic exposure to these proteins during clinical infection.
5248 24599530 The PAL-, PPP-, groES-, and ASS-specific responses were associated with secretion of functional Th1 (tumor necrosis factor alpha [TNF-α] and gamma interferon [IFN-γ]) and Th2 (interleukin 5 [IL-5] and IL-13) cytokines.
5249 24600553 After subcutaneous injection of fluorescein 5-isothiocyanate (FITC)-labeled NPs or FITC-ovalbumin (OVA)-carrying NPs (FITC-OVA-NPs), DCs migrated from the skin to the LNs and maturated, resulting in the upregulation of the costimulatory molecules CD80 and CD86 and the chemokine receptor CCR7.
5250 24600553 FITC-OVA-NPs were found to be taken up by skin-derived CD103(+) DCs, and the processed antigen peptides were cross-presented by the major histocompatibility complex (MHC) class I molecule of DCs.
5251 24600555 Here, we have addressed the effect of Tollip and MARCH1 on the regulation of MHC II trafficking and TLR signaling.
5252 24600555 Our results show that MARCH1-deficient mice splenocytes are impaired in their capacity to produce pro-inflammatory cytokines in response to poly(I:C) and that TLR3 and MHC II molecules interact in the endocytic pathway.
5253 24600555 Knocking down Tollip expression in human CIITA(+) HeLa cells increased expression of HLA-DR but reduced the proportion of MHC II molecules associated with the CLIP peptide.
5254 24600555 While overexpression of Tollip did not affect HLA-DR levels, it antagonized the function of co-transfected MARCH1.
5255 24600555 We found that Tollip strongly reduced MARCH1 protein levels and that the two molecules appear to compete for binding to MHC II molecules.
5256 24600555 Altogether, our results demonstrate that Tollip regulates MHC class II trafficking and that MARCH1 may represent a new Tollip target.
5257 24603870 An additional group of 16 MHC/KIR typed RM was included as controls.
5258 24606696 The peptides were shown to bind HLA-DRB1*0101 and then used to generate MHC II tetramers.
5259 24619686 In this chapter, we provide practical methods to create a potent in vivo tumor cell vaccine by inducing MHC Class II and Ii using MHC Class II transactivator (CIITA) or interferon-gamma (IFN-γ) and subsequently inhibiting Ii by antisense oligonucleotides.
5260 24675761 We identified a dominant HLA-A*0201-restricted epitope in the VZV ribonucleotide reductase subunit 2 and used a tetramer to analyze the phenotype and function of epitope-specific CD8 T cells.
5261 24682172 We have selected aptamers that specifically bind the murine receptor, DEC205, a C-type lectin expressed predominantly on the surface of CD8α(+) dendritic cells (DCs) that has been shown to be efficient at facilitating antigen crosspresentation and subsequent CD8(+) T cell activation.
5262 24682172 Using a minimized aptamer conjugated to the model antigen ovalbumin (OVA), DEC205-targeted antigen crosspresentation was verified in vitro and in vivo by proliferation and cytokine production by primary murine CD8(+) T cells expressing a T cell receptor specific for the major histocompatibility complex (MHC) I-restricted OVA257-264 peptide SIINFEKL.
5263 24682172 Compared with a nonspecific ribonucleic acid (RNA) of similar length, DEC205 aptamer-OVA-mediated antigen delivery stimulated strong proliferation and production of interferon (IFN)-γ and interleukin (IL)-2.
5264 24682434 HLA class I, KIR, and genome-wide SNP diversity in the RV144 Thai phase 3 HIV vaccine clinical trial.
5265 24682434 Human leukocyte antigen (HLA) class I and killer cell immunoglobulin-like receptor (KIR) genes, as well as 96 genome-wide ancestry informative markers (AIMs) were genotyped in 450 placebo HIV-1-uninfected individuals to identify the immunogenetic diversity and population structure of this cohort.
5266 24682434 Framework genes KIR2DL4, 3DL2, and 3DL3 were present in all samples, and KIR2DL1, 2DL3, 3DL1, 2DS4, and 2DP1 occurred at frequencies greater than 90 %.
5267 24682434 HLA class I, KIR, and genome-wide SNP diversity in the RV144 Thai phase 3 HIV vaccine clinical trial.
5268 24682434 Human leukocyte antigen (HLA) class I and killer cell immunoglobulin-like receptor (KIR) genes, as well as 96 genome-wide ancestry informative markers (AIMs) were genotyped in 450 placebo HIV-1-uninfected individuals to identify the immunogenetic diversity and population structure of this cohort.
5269 24682434 Framework genes KIR2DL4, 3DL2, and 3DL3 were present in all samples, and KIR2DL1, 2DL3, 3DL1, 2DS4, and 2DP1 occurred at frequencies greater than 90 %.
5270 24688455 GM-CSF signaling was identified as the most potent chemotactic factor for conventional DCs and significantly enhanced surface expression of MHC(II) and CD86(+), which are utilized for priming T cell immunity.
5271 24690990 Immunization with a peptide containing MHC class I and II epitopes derived from the tumor antigen SIM2 induces an effective CD4 and CD8 T-cell response.
5272 24690990 Here, we sought to determine whether peptide vaccines designed harbor both class I as well as class II restricted antigenic motifs could concurrently induce CD4 and CD8 T cell activation against autologous tumor antigens.
5273 24690990 Immunization with a multi-epitope peptide harboring both MHC-I and MHC-II restricted epitopes induced an IFN-γ response in CD8 T cells to the HLA-A*0201-restricted SIM2(237-245) epitope, and an IL-2 response by CD4 T cells to the SIM2(240-254) epitope.
5274 24690990 Collectively, the data presented in this study suggest that a single peptide containing multiple SIM2 epitopes can be used to induce both a CD4 and CD8 T cell response, providing a peptide-based vaccine formulation for potential use in immunotherapy of various cancers.
5275 24690990 Immunization with a peptide containing MHC class I and II epitopes derived from the tumor antigen SIM2 induces an effective CD4 and CD8 T-cell response.
5276 24690990 Here, we sought to determine whether peptide vaccines designed harbor both class I as well as class II restricted antigenic motifs could concurrently induce CD4 and CD8 T cell activation against autologous tumor antigens.
5277 24690990 Immunization with a multi-epitope peptide harboring both MHC-I and MHC-II restricted epitopes induced an IFN-γ response in CD8 T cells to the HLA-A*0201-restricted SIM2(237-245) epitope, and an IL-2 response by CD4 T cells to the SIM2(240-254) epitope.
5278 24690990 Collectively, the data presented in this study suggest that a single peptide containing multiple SIM2 epitopes can be used to induce both a CD4 and CD8 T cell response, providing a peptide-based vaccine formulation for potential use in immunotherapy of various cancers.
5279 24695530 During the acute phase of infection, IL-10 correlated positively with viral load and negatively with CD4+T cell counts.
5280 24695530 These data indicate that the MHC could contribute to the delicate balance of pro-inflammatory mechanisms, particularly with regard to the association between IL-10 and α-defensins in lentivirus infection.
5281 24709642 Peptide specific CD8+ human T cell lines from peripheral blood lymphocytes were generated from a HLA-A*02+ donor.
5282 24709642 High frequencies of peptide specific CD8+ T cell responses were elicited in mice by DNA vaccination with ICP27, VP22 and VP13/14, as demonstrated by CD107a mobilization.
5283 24721533 Spontaneous resolution of infection is associated with broad, MHC class I- (CD8(+)) and class II-restricted (CD4(+)) T cell responses to multiple viral epitopes.
5284 24724694 As experimentally mapping an optimal CD8 T-cell epitope is a tedious procedure, many bioinformatic tools have been developed that predict which peptides bind to a given MHC molecule.
5285 24726370 One key question is why CD8(+) T cell responses to two HIV-Gag regions are uniquely associated with delayed disease progression only in patients expressing a few rare HLA class I variants when these regions encode epitopes presented by ~30 more common HLA variants.
5286 24727060 It is thought that c-di-GMP is recognized by ATP dependent RNA helicase (DDX41) in the cytosol, forms a complex with the Stimulator of interferon genes protein (STING), triggers a signal via the tank binding kinase 1-interferon regulatory factor 3 (TBK1-IRF3) pathway and induces the production of type I interferons.
5287 24727060 C-di-GMP liposomes also showed significantly higher levels of expression of CD80, CD86 and MHC class I.
5288 24736000 We created and produced a novel self-assembling nanoparticle platform for delivery of peptide epitopes that induces CD8(+) and CD4(+)T cells that are protective against Toxoplasma gondii infection.
5289 24736000 This work demonstrates the feasibility of using this platform approach with a CD8(+) epitope that binds HLA-B7 and tests the biological activity of potentially protective peptides restricted by human major histocompatibility complex (HLA) class I molecules in HLA transgenic mice.
5290 24738485 In macrophages, HBsAg adsorbed on the surface of cationic microspheres specifically enhanced antigen uptake and augmented CD86, MHC I, and MHC II expression and IL-1β, IL-6, TNF-α, and IL-12 release.
5291 24743648 In this study, we characterized the phenotypic and functional differences between dominant and subdominant simian immunodeficiency virus (SIV) epitope-specific CD8+ T cells restricted by the major histocompatibility complex (MHC) class I allele Mamu-A*01 during acute and chronic SIV infection.
5292 24743648 Expression analyses of exhaustion-associated genes indicated that LAG-3 and CTLA-4 were more highly expressed in the dominant epitope-specific cells during acute SIV infection.
5293 24743648 These studies demonstrate that significant functional differences exist between dominant and subdominant epitope-specific CD8+ T cells within MHC-restricted immunodominance hierarchies and suggest that TCR:pMHC affinity may play an important role in determining the frequency and functionality of these cell populations.
5294 24743648 In this study, we characterized the phenotypic and functional differences between dominant and subdominant simian immunodeficiency virus (SIV) epitope-specific CD8+ T cells restricted by the major histocompatibility complex (MHC) class I allele Mamu-A*01 during acute and chronic SIV infection.
5295 24743648 Expression analyses of exhaustion-associated genes indicated that LAG-3 and CTLA-4 were more highly expressed in the dominant epitope-specific cells during acute SIV infection.
5296 24743648 These studies demonstrate that significant functional differences exist between dominant and subdominant epitope-specific CD8+ T cells within MHC-restricted immunodominance hierarchies and suggest that TCR:pMHC affinity may play an important role in determining the frequency and functionality of these cell populations.
5297 24744786 We have found the role of specific HLA supertypes such as HLA B∗07, HLA B∗58, and HLA A∗03 in selecting the hydrophobic and conserved amino acid positions within Nef and Gag proteins, to be presented as epitopes.
5298 24744786 The analyses revealed that the clusters of optimal epitopes for Nef and p24 proteins of HIV-1 could potentially serve as a source of vaccine.
5299 24761845 The surface expression of CD40, CD68, MHC II and CD11c was assessed by flow cytometry (FCM), and the lethal effects of CTL against CaSki cells were determined by DAPI, FCM and CCK-8 methods.
5300 24775445 In addition, Tp587-95 specific bovine CTL were simultaneously stained by Tp5-BoLA-1*02301 and Tp5-BoLA-T5 tetramers suggesting that one T cell receptor can bind to two different BoLA MHC class I molecules presenting the Tp587-95 epitope and that these BoLA molecules fall into a single functional supertype.
5301 24789782 The data obtained with overlapping peptides in interleukin-2 (IL-2) enzyme-linked immunosorbent spot (ELISpot) assays were analyzed in relation to the three-dimensional structures of the capsid (C) and E proteins as well as to epitope predictions based on major histocompatibility complex (MHC) class II peptide affinities.
5302 24789790 The human immunodeficiency virus type 1 (HIV-1) accessory protein Nef is heavily targeted by CD8(+) T lymphocytes (CTLs) during acute infection and therefore is included in many candidate vaccines.
5303 24789790 Nef-mediated downregulation of CD4 and major histocompatibility complex (MHC) class I molecules was better preserved in acute infection than in chronic infection.
5304 24790732 MHC class I antigen presentation and implications for developing a new generation of therapeutic vaccines.
5305 24790791 We generated a number of minigenes containing epitopes from the carcinoembryonic antigen (CEA) model TAA and utilized muscle DNA electro-gene-transfer (DNA-EGT) to vaccinate HLA-A*0201 (HHD) and CEA/HHD double transgenic mice.
5306 24790791 Other candidate components comparatively tested included: helper CD4+ T-cell epitopes, flanking regions for optimal epitope processing (including both proteasome-dependent and furin-dependent polypeptide processing mechanisms), and immunoenhancing moieties.
5307 24790791 Through a series of comparative studies and iterations we have identified an optimal minigene scaffold comprising the following elements: human tissue plasminogen activator (TPA) signal peptide, T-cell epitopes connected by furin sensitive linkers, and the E.
5308 24790791 The selected epitope modified minigenes (EMM) delivered by DNA-EGT were able to break immune tolerance in CEA/HHD mice and induce a strong immune response against all epitopes tested, independently of their relative positions within the scaffold.
5309 24794408 We identified novel helper epitope peptides of Survivin cancer antigen, which are presented to both HLA-DRB1*01:01 and DQB1*06:01.
5310 24794408 The helper epitope also contained three distinct Survivin-killer epitopes presented to HLA-A*02:01 and A*24:02.
5311 24794408 This 19 amino-acids epitope peptide (SU18) induced weak responses of Survivin-specific CD4(+) and CD8(+) T cells though it contained both helper and killer epitopes.
5312 24794408 Survivin-H/K-HELP allowed superior activation of IFN-γ-producing CD4(+) Th1 cells and CD8(+) Tc1 cells compared with the mixture of its component peptides (SU18 and SU22) in the presence of OK-432-treated monocyte-derived DC (Mo-DC).
5313 24795724 Research in mouse models has highly enhanced our understanding of the mechanisms underlying cross-presentation and the dendritic cells (DC) subsets involved, however, these results cannot be readily translated toward the role of human DC in MHC class I-antigen presentation of human viruses.
5314 24798939 Associations of HLA-A, HLA-B and HLA-C alleles frequency with prevalence of herpes simplex virus infections and diseases across global populations: implication for the development of an universal CD8+ T-cell epitope-based vaccine.
5315 24798939 The present report: (i) analyzes the prevalence of HSV-1 and HSV-2 infections across various regions of the world; (ii) analyzes potential associations of common HLA-A, HLA-B and HLA-C alleles with the prevalence of HSV-1 and HSV-2 infections in the Caucasoid, Oriental, Hispanic and Black major populations; and (iii) discusses how our recently developed HLA-A, HLA-B, and HLA-C transgenic/H-2 class I null mice will help validate HLA/herpes prevalence associations.
5316 24798939 Overall, high prevalence of herpes infection and disease appears to be associated with high frequency of HLA-A(∗)24, HLA-B(∗)27, HLA-B(∗)53 and HLA-B(∗)58 alleles.
5317 24798939 Associations of HLA-A, HLA-B and HLA-C alleles frequency with prevalence of herpes simplex virus infections and diseases across global populations: implication for the development of an universal CD8+ T-cell epitope-based vaccine.
5318 24798939 The present report: (i) analyzes the prevalence of HSV-1 and HSV-2 infections across various regions of the world; (ii) analyzes potential associations of common HLA-A, HLA-B and HLA-C alleles with the prevalence of HSV-1 and HSV-2 infections in the Caucasoid, Oriental, Hispanic and Black major populations; and (iii) discusses how our recently developed HLA-A, HLA-B, and HLA-C transgenic/H-2 class I null mice will help validate HLA/herpes prevalence associations.
5319 24798939 Overall, high prevalence of herpes infection and disease appears to be associated with high frequency of HLA-A(∗)24, HLA-B(∗)27, HLA-B(∗)53 and HLA-B(∗)58 alleles.
5320 24798939 Associations of HLA-A, HLA-B and HLA-C alleles frequency with prevalence of herpes simplex virus infections and diseases across global populations: implication for the development of an universal CD8+ T-cell epitope-based vaccine.
5321 24798939 The present report: (i) analyzes the prevalence of HSV-1 and HSV-2 infections across various regions of the world; (ii) analyzes potential associations of common HLA-A, HLA-B and HLA-C alleles with the prevalence of HSV-1 and HSV-2 infections in the Caucasoid, Oriental, Hispanic and Black major populations; and (iii) discusses how our recently developed HLA-A, HLA-B, and HLA-C transgenic/H-2 class I null mice will help validate HLA/herpes prevalence associations.
5322 24798939 Overall, high prevalence of herpes infection and disease appears to be associated with high frequency of HLA-A(∗)24, HLA-B(∗)27, HLA-B(∗)53 and HLA-B(∗)58 alleles.
5323 24824351 We identified and chose HLA-A*0201-binding peptides from human HSPB1 (HSP27) and HSP90AA1 (HSP90), and confirmed their immunogenicity in HLA-A*0201 transgenic mice.
5324 24824351 Dendritic cells pulsed with HSPB1 and HSP90AA1 peptides were used to stimulate peripheral blood mononuclear cells from healthy volunteers and myeloma patients to generate HSP peptide-specific cytotoxic T lymphocytes (CTLs).
5325 24824351 HSP peptide-specific CTLs efficiently lysed HLA-A*0201(+) myeloma cells (established cell lines and primary plasma cells) but not HLA-A*0201(-) myeloma cells in vitro, indicating that myeloma cells naturally express HSP peptides in the context of major histocompatibility complex class I molecules.
5326 24824351 We identified and chose HLA-A*0201-binding peptides from human HSPB1 (HSP27) and HSP90AA1 (HSP90), and confirmed their immunogenicity in HLA-A*0201 transgenic mice.
5327 24824351 Dendritic cells pulsed with HSPB1 and HSP90AA1 peptides were used to stimulate peripheral blood mononuclear cells from healthy volunteers and myeloma patients to generate HSP peptide-specific cytotoxic T lymphocytes (CTLs).
5328 24824351 HSP peptide-specific CTLs efficiently lysed HLA-A*0201(+) myeloma cells (established cell lines and primary plasma cells) but not HLA-A*0201(-) myeloma cells in vitro, indicating that myeloma cells naturally express HSP peptides in the context of major histocompatibility complex class I molecules.
5329 24846569 Pretreatment with WapA-GST also increased LPS-induced proinflammatory cytokine production by DCs, including IL-12, IL-6 and TNF-α.
5330 24846569 Furthermore, expression of the DC maturation markers CD80/86, CD40 and MHC II was also increased by WapA pretreatment.
5331 24852051 Antigens for CD4 and CD8 T cells in tuberculosis.
5332 24852051 CD4(+) and CD8(+) T cells play an important role in host defense to TB.
5333 24852051 Herein, the antigens and epitopes recognized by classically HLA class I- and II-restricted CD4(+) and CD8(+) T cells in humans infected with MTB are reviewed.
5334 24852051 Antigens and epitopes recognized by classically restricted CD4(+) and CD8(+) T cells show extensive breadth and diversity in MTB-infected humans.
5335 24854165 To follow the fate of CD8+ T cells responsive to Plasmodium berghei ANKA (PbA) infection, we generated an MHC I-restricted TCR transgenic mouse line against this pathogen.
5336 24861251 The functional maturation was confirmed by an acid phosphatase (ACP) activity test, FITC-dextran bio-assay, test of 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE), labeled CD4(+)T cell proliferation and enzyme-linked immunosorbent assay (ELISA).
5337 24861251 We determined that thymopentin up-regulated the expression of CD40, CD80, CD86, CD83, and MHC II molecules on BMDCs, down-regulated phagocytosis of BMDCs, increased BMDCs driven CD4(+)T cell proliferation, and enhanced BMDC production of IL-12 and TNF-α.
5338 24866397 Using the early protein HIV Nef, new HLA class I binding epitopes of importance for immune responses to HIV were predicted for common African alleles.
5339 24894091 Immunohistochemical data of infiltrating (suppressive) cells, such as T cells, regulatory T cells, myeloid-derived suppressor cells, and mast cells, or the expression of T-cell inhibitory factors (PD-1/PD-L1, IDO, and galectins), cytotoxic molecules (granzyme-B), melanocyte differentiation antigens, HLA class-I and tolerogenic cytokines [interleukin (IL)-1, IL-6, IL-10, TNF-α, and TGF-β] were correlated statistically to clinical outcome and overall survival (OS).
5340 24894091 Significantly more tumor-infiltrating CD4(+) and CD8(+) T cells (both P < 0.05) were found in nonprogressors to vaccination (n = 9; median OS, 56 months), compared with progressors (n = 18; median OS, 9.5 months).
5341 24894091 Our study shows that high numbers of intratumoral activated CD4(+) or CD8(+) T cells, before autologous tumor cell vaccination, are associated with favorable clinical outcome.
5342 24915083 In order to clarify the structural characteristics of the bovine MHC class I molecule (BoLA-I) complexed with CD8αα (CD8αα-BoLA-I), bovine CD8αα, BoLA-I (BoLA-2*02201) and β2m were expressed and purified, and were then assembled with a peptide derived from Foot-and-mouth disease virus (FMDV-VP1YY9) and crystallized.
5343 24942994 We hereby proved that LJP markedly induced maturation of BMDCs with the data of decreased the number of lysosomes, upregulated expression of CD80, CD83, CD86, CD40 and MHC II key membrane molecules on BMDCs, downregulated phagocytosis, enriched production of IL-12 and TNF-α secreted by BMDCs.
5344 24962751 The results demonstrated that rTs-Hsp70 activated DC maturation that was characterized by the secretion of IL-1β, IL-12p70, TNF-α, and IL-6 and the increased surface expression of CD11c, MHC II, CD40, CD80, and CD86.
5345 24962751 The rTs-Hsp70-activated DCs enabled the stimulation, proliferation and secretion of Th1/2 cytokines (i.e., INF-γ, IL-2, IL-4 and IL-6) in CD4(+) T cells from T. spiralis-infected mice.
5346 24962751 This partial protection was correlated with Th1 and Th2 mixed anti-Ts-Hsp70-specific immune responses that included high titers of total IgG, IgG1 and IgG2a and increased levels of Th1/2 cytokines (i.e., IFN-γ, IL-2, IL-4, IL-6).
5347 24983460 We found that a peptide containing QNT-5 was able to elicit long-term anti-CS Ab responses and prime CD4 T cells in HLA-DR4 transgenic mice despite forming relatively unstable MHC-peptide complexes highly susceptible to HLA-DM editing.
5348 24983460 The modified peptide QNT-Y formed stable MHC-peptide complexes highly resistant to HLA-DM editing.
5349 24983460 We found that a peptide containing QNT-5 was able to elicit long-term anti-CS Ab responses and prime CD4 T cells in HLA-DR4 transgenic mice despite forming relatively unstable MHC-peptide complexes highly susceptible to HLA-DM editing.
5350 24983460 The modified peptide QNT-Y formed stable MHC-peptide complexes highly resistant to HLA-DM editing.
5351 24995346 Distribution of HLA-A, -B, and -C alleles and HLA/KIR combinations in Han population in China.
5352 24995346 A total of 27 HLA-A, 54 HLA-B, and 31 HLA-C alleles were found in this population.
5353 24995346 The results of KIR/HLA-C combination analysis showed that all individuals had at least one inhibitory or activating KIR/HLA-C pair, and one KIR/HLA-C pair was the most frequent (157/239), followed by two pairs (46/239), three pairs (33/239), and no pairs (3/239).
5354 24995346 Distribution of HLA-A, -B, and -C alleles and HLA/KIR combinations in Han population in China.
5355 24995346 A total of 27 HLA-A, 54 HLA-B, and 31 HLA-C alleles were found in this population.
5356 24995346 The results of KIR/HLA-C combination analysis showed that all individuals had at least one inhibitory or activating KIR/HLA-C pair, and one KIR/HLA-C pair was the most frequent (157/239), followed by two pairs (46/239), three pairs (33/239), and no pairs (3/239).
5357 24998253 Cell clusters within these FTAs can be pulsed with major histocompatibility (MHC) class-I and MHC class-II binding peptides and thereby act as target cells for CD8(+) and CD4(+) T cells, respectively.
5358 24998253 These FTA cells remain viable and fully functional, and can therefore be administered into mice to allow assessment of CD8(+) T cell-mediated killing of FTA target cells and CD4(+) T cell-meditated help of FTA B cell target cells in real time in vivo by flow cytometry.
5359 25008925 Impact of sequence variation in a dominant HLA-A*02-restricted epitope in hepatitis C virus on priming and cross-reactivity of CD8+ T cells.
5360 25013909 Intraperitoneal administration of a tumor-associated antigen SART3, CD40L, and GM-CSF gene-loaded polyplex micelle elicits a vaccine effect in mouse tumor models.
5361 25013909 Here, we investigated a polyplex micelle encapsulating genes encoding the tumor-associated antigen squamous cell carcinoma antigen recognized by T cells-3 (SART3), adjuvant CD40L, and granulocyte macrophage colony-stimulating factor (GM-CSF) as a DNA vaccine platform in mouse tumor models with different types of major histocompatibility antigen complex (MHC).
5362 25013909 The DNA vaccine highly stimulated both cytotoxic T lymphocyte and natural killer cell activities, and increased the infiltration of CD11c+ DCs and CD4+/CD8a+ T cells into tumors.
5363 25013909 Depletion of CD4+ or CD8a+ T cells by neutralizing antibodies deteriorated the anti-tumor efficacy of the DNA vaccine.
5364 25013909 In conclusion, a SART3/CD40L+GM-CSF gene-loaded polyplex micelle can be applied as a novel vaccine platform to elicit tumor rejection immunity regardless of the recipient MHC haplotype.
5365 25013909 Intraperitoneal administration of a tumor-associated antigen SART3, CD40L, and GM-CSF gene-loaded polyplex micelle elicits a vaccine effect in mouse tumor models.
5366 25013909 Here, we investigated a polyplex micelle encapsulating genes encoding the tumor-associated antigen squamous cell carcinoma antigen recognized by T cells-3 (SART3), adjuvant CD40L, and granulocyte macrophage colony-stimulating factor (GM-CSF) as a DNA vaccine platform in mouse tumor models with different types of major histocompatibility antigen complex (MHC).
5367 25013909 The DNA vaccine highly stimulated both cytotoxic T lymphocyte and natural killer cell activities, and increased the infiltration of CD11c+ DCs and CD4+/CD8a+ T cells into tumors.
5368 25013909 Depletion of CD4+ or CD8a+ T cells by neutralizing antibodies deteriorated the anti-tumor efficacy of the DNA vaccine.
5369 25013909 In conclusion, a SART3/CD40L+GM-CSF gene-loaded polyplex micelle can be applied as a novel vaccine platform to elicit tumor rejection immunity regardless of the recipient MHC haplotype.
5370 25040249 Additionally, minimal variation in known antigenic epitopes for the HLA-A 02 allele suggests that interlineage variation in TSA-1 would not impair the range and efficacy of a vaccine containing TSA-1.
5371 25043048 Monoallelic point mutations of isocitrate dehydrogenase type 1 (IDH1) are an early and defining event in the development of a subgroup of gliomas and other types of tumour.
5372 25043048 Peptides encompassing the mutated region are presented on major histocompatibility complexes (MHC) class II and induce mutation-specific CD4(+) T-helper-1 (TH1) responses.
5373 25043048 CD4(+) TH1 cells and antibodies spontaneously occurring in patients with IDH1(R132H)-mutated gliomas specifically recognize IDH1(R132H).
5374 25043048 Peptide vaccination of mice devoid of mouse MHC and transgenic for human MHC class I and II with IDH1(R132H) p123-142 results in an effective MHC class II-restricted mutation-specific antitumour immune response and control of pre-established syngeneic IDH1(R132H)-expressing tumours in a CD4(+) T-cell-dependent manner.
5375 25043048 Monoallelic point mutations of isocitrate dehydrogenase type 1 (IDH1) are an early and defining event in the development of a subgroup of gliomas and other types of tumour.
5376 25043048 Peptides encompassing the mutated region are presented on major histocompatibility complexes (MHC) class II and induce mutation-specific CD4(+) T-helper-1 (TH1) responses.
5377 25043048 CD4(+) TH1 cells and antibodies spontaneously occurring in patients with IDH1(R132H)-mutated gliomas specifically recognize IDH1(R132H).
5378 25043048 Peptide vaccination of mice devoid of mouse MHC and transgenic for human MHC class I and II with IDH1(R132H) p123-142 results in an effective MHC class II-restricted mutation-specific antitumour immune response and control of pre-established syngeneic IDH1(R132H)-expressing tumours in a CD4(+) T-cell-dependent manner.
5379 25049333 Mucosal-associated invariant T (MAIT) cells express a semi-invariant T cell receptor (TCR) that detects microbial metabolites presented by the nonpolymorphic major histocompatibility complex (MHC)-like molecule MR1.
5380 25080481 Both BDCA3(+) and monocyte-derived DC-SIGN(+) NP-loaded DCs were equally effective at generating Ag-specific human T cells in culture, including against complex peptide mixtures from viral and tumor Ags across multiple MHC molecules.
5381 25111185 Peptide-specific IFN-γ production by splenic T cells obtained at 5 weeks post-immunization was quantified by ELISpot assay; additionally, the production of IL-4, IL-10 and TNF-α were quantified by cytokine bead array.
5382 25111185 Splenocytes derived from vaccinated HLA-A2/DRB1 transgenic mice exhibited peptide-specific cytokine production to the vast majority of the vaccine-encoded HLA class I- and class II-restricted T cell epitopes.
5383 25122197 Increased generation of HIV-1 gp120-reactive CD8+ T cells by a DNA vaccine construct encoding the chemokine CCL3.
5384 25122197 Two molecules were tested for their efficiency as targeting units: the antibody-derived single chain Fragment variable (scFv) specific for the major histocompatibility complex (MHC) class II I-E molecules, and the CC chemokine ligand 3 (CCL3).
5385 25122197 Targeting by CCL3 significantly increased the number of HIV-1 gp120-reactive CD8+ T cells compared to non-targeted vaccines and gp120 delivered alone in the absence of electroporation.
5386 25173989 Mucosal-associated invariant T (MAIT) cells are a recently discovered population of unconventional T cells characterized by an evolutionarily conserved αβ T cell receptor (TCR) that recognizes antigens presented by major histocompatibility complex (MHC) class I-related (MR1) molecule.
5387 25186612 Compared to the native epitope, the agonist epitope: (a) has enhanced binding to MHC class I, (b) increased the IFN-γ production from brachyury-specific T cells, (c) generated brachyury-specific T cells with greater levels of perforin and increased proliferation, (d) generated T cells more proficient at lysing human carcinoma cells endogenously expressing the native epitope, and (e) achieved greater brachyury-specific T-cell responses in vivo in HLA-A2 transgenic mice.
5388 25193656 Nef-mediated down-regulation of CD4 and HLA class I in HIV-1 subtype C infection: association with disease progression and influence of immune pressure.
5389 25202304 The CD8(+) T cell-mediated protective immune response against CSP is dependent on the interleukin loop involving IL-4 receptor expression on CD8(+) cells and IL-4 secretion by CD4(+) T cell helpers.
5390 25202304 In the liver, the hepatic sinusoids are enriched with cells, such as dendritic, sinusoidal endothelial and Kupffer cells, that are able to cross-present MHC class I antigens to intrahepatic CD8(+) T cells.
5391 25207820 These expansions were enriched with human papillomavirus 16 (HPV16)-specific CD8+ T cells in HLA-A*0201+ patients as shown by their immune recognition of the E711-20 immunodominant epitope.
5392 25218300 High expression of MAGE-A4 and MHC class I antigens in tumor cells and induction of MAGE-A4 immune responses are prognostic markers of CHP-MAGE-A4 cancer vaccine.
5393 25225119 We found that CTS downregulated the numbers of phagosomes inside the BMDCs, up-regulated the expression of MHC II, CD40, CD83, CD80 and CD86 molecules on BMDCs, decreased activity of ACP and phagocytosis by BMDCs, and induced production of higher levels of IL-12 and TNF-α.
5394 25257859 PolyI:C and mouse survivin artificially embedding human 2B peptide induce a CD4+ T cell response to autologous survivin in HLA-A*2402 transgenic mice.
5395 25257859 The chimeric survivin, where human survivin-2B containing a TAA was embedded in the mouse survivin frame (MmSVN2B), was used to immunize HLA-A-2402/K(b)-transgenic (HLA24(b)-Tg) mice.
5396 25257859 Although HLA-A-2402/K(b) presented the survivin-2B peptide in C57BL/6 mice, 2B-specific tetramer assays showed that no CD8(+) T CTLs specific to survivin-2B proliferated above the detection limit in immunized mice, even with polyI:C treatment.
5397 25257859 The CD4 epitope responsible for effector function was not Hs/MmSNV13-27, a nonconserved region between human and mouse survivin, but region 53-67, which was identical between human and mouse survivin.
5398 25257859 PolyI:C and mouse survivin artificially embedding human 2B peptide induce a CD4+ T cell response to autologous survivin in HLA-A*2402 transgenic mice.
5399 25257859 The chimeric survivin, where human survivin-2B containing a TAA was embedded in the mouse survivin frame (MmSVN2B), was used to immunize HLA-A-2402/K(b)-transgenic (HLA24(b)-Tg) mice.
5400 25257859 Although HLA-A-2402/K(b) presented the survivin-2B peptide in C57BL/6 mice, 2B-specific tetramer assays showed that no CD8(+) T CTLs specific to survivin-2B proliferated above the detection limit in immunized mice, even with polyI:C treatment.
5401 25257859 The CD4 epitope responsible for effector function was not Hs/MmSNV13-27, a nonconserved region between human and mouse survivin, but region 53-67, which was identical between human and mouse survivin.
5402 25257859 PolyI:C and mouse survivin artificially embedding human 2B peptide induce a CD4+ T cell response to autologous survivin in HLA-A*2402 transgenic mice.
5403 25257859 The chimeric survivin, where human survivin-2B containing a TAA was embedded in the mouse survivin frame (MmSVN2B), was used to immunize HLA-A-2402/K(b)-transgenic (HLA24(b)-Tg) mice.
5404 25257859 Although HLA-A-2402/K(b) presented the survivin-2B peptide in C57BL/6 mice, 2B-specific tetramer assays showed that no CD8(+) T CTLs specific to survivin-2B proliferated above the detection limit in immunized mice, even with polyI:C treatment.
5405 25257859 The CD4 epitope responsible for effector function was not Hs/MmSNV13-27, a nonconserved region between human and mouse survivin, but region 53-67, which was identical between human and mouse survivin.
5406 25268942 CD8(+) T cells identify and kill infected cells through the specific recognition of short viral antigens bound to human major histocompatibility complex (HLA) class I molecules.
5407 25272598 Meanwhile, pJME/GM-CSF increased the expression of MHC class II molecules on splenic DCs, and enhanced their Ag capture and presentation functions.
5408 25279150 Induction of HLA-A*33-restricted cytotoxic lymphocytes against renal cell carcinoma targeting galectin 9 and PINCH.
5409 25279150 Galectin 9, a ligand of T cell immunoglobulin and mucin domain 3 (TIM-3), and PINCH, an epithelial-to-mesenchymal transition (EMT)-promoting molecule, are expressed at much higher levels in cancerous lesions of clear cell type renal cell carcinoma (RCC) compared to normal renal tissues, and their expression levels are extremely low in normal tissues, except for galectin 9 in the spleen.
5410 25279150 Galectin 9- and PINCH-derived peptides have previously been shown to induce human leukocyte antigen (HLA)-A*2402-restricted and HLA-A*0201-restricted cytotoxic lymphocytes (CTLs) with specific and highly cytotoxic activities toward RCC cells.
5411 25279150 Induction of HLA-A*33-restricted cytotoxic lymphocytes against renal cell carcinoma targeting galectin 9 and PINCH.
5412 25279150 Galectin 9, a ligand of T cell immunoglobulin and mucin domain 3 (TIM-3), and PINCH, an epithelial-to-mesenchymal transition (EMT)-promoting molecule, are expressed at much higher levels in cancerous lesions of clear cell type renal cell carcinoma (RCC) compared to normal renal tissues, and their expression levels are extremely low in normal tissues, except for galectin 9 in the spleen.
5413 25279150 Galectin 9- and PINCH-derived peptides have previously been shown to induce human leukocyte antigen (HLA)-A*2402-restricted and HLA-A*0201-restricted cytotoxic lymphocytes (CTLs) with specific and highly cytotoxic activities toward RCC cells.
5414 25282505 Here we describe a new and highly efficient antipneumococcal vaccine design based on synthetic conjugation of S. pneumoniae capsule polysaccharides to the potent lipid antigen α-galactosylceramide, which stimulates invariant natural killer T (iNKT) cells when presented by the nonpolymorphic antigen-presenting molecule CD1d.
5415 25295286 Similarities included specialties of referring physicians, mean ages, proportions of women, reactivity to Pneumovax, median serum IgG3 and IgG4 levels, median blood CD56+/CD16+ lymphocyte levels, positivity for HLA-A and -B types, and frequencies of selected HLA-A, -B haplotypes.
5416 25295286 Dissimilarities included greater prevalence of autoimmune conditions, lower median IgG, IgA, and IgM, and lower median CD19+, CD3+/CD4+, and CD3+/CD8+ blood lymphocytes in CVID patients.
5417 25295286 Logistic regression on CVID (versus IgGSD) revealed a significant positive association with autoimmune conditions and significant negative associations with IgG1, IgG3, and IgA and CD56+/CD16+ lymphocyte levels, but the odds ratio was increased for autoimmune conditions alone (6.9 (95% CI 1.3, 35.5)).
5418 25299691 Interestingly, muscle fibers that produced MHC class II-specific dimeric vaccine proteins with mCherry were for weeks surrounded by a localized intense cellular infiltrate composed of CD45+, MHC class II+ and CD11b+ cells.
5419 25356981 The slope of the trajectory offers an interpretation of positive correlation between fitness costs and HLA binding impairment to HLA-A molecules and a protective subset of HLA-B molecules that was observed for clinically relevant escape mutations in the Pol gene.
5420 25387894 The augmentation of high-titer antibodies to ATP6S1 is associated with favorable clinical outcomes in patients who received vaccination with autologous, irradiated tumor cells engineered to secrete GM-CSF and allogeneic bone marrow transplantation.
5421 25387894 Recombinant ATP6S1 protein was used in an ELISA to assess potential correlation with humoral immune responses and changes in immunity related to CTLA-4 blockade with ipilimumab in these patients.
5422 25387894 We observed a broad array of CD4(+) and CD8(+) cellular responses against ATP6S1, including the identification of several MHC class I and II ATP6S1 epitopes.
5423 25457547 The swine major histocompatibility complex (MHC) genomic region (SLA) is extremely polymorphic comprising high numbers of different alleles, many encoding a distinct MHC class I molecule, which binds and presents endogenous peptides to circulating T cells of the immune system.
5424 25471691 The best-studied system to date is the decamer MART-1/Melan-A26-35 peptide, EAAGIGILTV, where the natural alanine at position 2 has been modified to leucine to improve human leukocyte antigen (HLA)-A*0201 anchoring.
5425 25482339 For protein-based vaccines, the main biological barrier to overcome is the default MHC class-II-pathway, with activation of CD4 T cells rather than CD8 T cells.
5426 25482339 The latter requires antigens to access the cytosol and MHC class I antigen presentation.
5427 25482339 This "photochemical internalisation" resulted in activation, proliferation, and IFN-γ production of cytotoxic CD8 T cells, which suppressed tumour growth by infiltrating CD8 T cells and caspase-3-dependent apoptosis.
5428 25482339 The process was independent of MHC class II, MyD88, and TLR4 signalling, but dependent on trypsin- and caspase-like proteasome activity and partly also on chloroquine.
5429 25482339 For protein-based vaccines, the main biological barrier to overcome is the default MHC class-II-pathway, with activation of CD4 T cells rather than CD8 T cells.
5430 25482339 The latter requires antigens to access the cytosol and MHC class I antigen presentation.
5431 25482339 This "photochemical internalisation" resulted in activation, proliferation, and IFN-γ production of cytotoxic CD8 T cells, which suppressed tumour growth by infiltrating CD8 T cells and caspase-3-dependent apoptosis.
5432 25482339 The process was independent of MHC class II, MyD88, and TLR4 signalling, but dependent on trypsin- and caspase-like proteasome activity and partly also on chloroquine.
5433 25482339 For protein-based vaccines, the main biological barrier to overcome is the default MHC class-II-pathway, with activation of CD4 T cells rather than CD8 T cells.
5434 25482339 The latter requires antigens to access the cytosol and MHC class I antigen presentation.
5435 25482339 This "photochemical internalisation" resulted in activation, proliferation, and IFN-γ production of cytotoxic CD8 T cells, which suppressed tumour growth by infiltrating CD8 T cells and caspase-3-dependent apoptosis.
5436 25482339 The process was independent of MHC class II, MyD88, and TLR4 signalling, but dependent on trypsin- and caspase-like proteasome activity and partly also on chloroquine.
5437 25516422 Using a novel sequence based MHC class I typing method, we found no association of BNP with MHC class I haplotype distribution in dams or calves.
5438 25523015 Within these TAAs are peptide sequences that bind major histocompatibility complex (MHC) class I and class II molecules recognized by T cells triggering antigen-specific CD8+ cytotoxic T-cell and CD4+ T-helper cell responses.
5439 25523015 The majority of vaccine trials have used peptides, including single-peptide and multiple-peptide formulations using either MHC class I and class II epitopes in oil-based emulsions alone or in combination with an adjuvant, such as granulocyte-macrophage colony-stimulating factor, and Toll-like receptor agonists.
5440 25523015 Within these TAAs are peptide sequences that bind major histocompatibility complex (MHC) class I and class II molecules recognized by T cells triggering antigen-specific CD8+ cytotoxic T-cell and CD4+ T-helper cell responses.
5441 25523015 The majority of vaccine trials have used peptides, including single-peptide and multiple-peptide formulations using either MHC class I and class II epitopes in oil-based emulsions alone or in combination with an adjuvant, such as granulocyte-macrophage colony-stimulating factor, and Toll-like receptor agonists.
5442 25613992 HIV-1 develops specific mutations within its genome that allow it to escape detection by human leukocyte antigen (HLA) class I-restricted immune responses, notably those of CD8(+) cytotoxic T lymphocytes (CTL).
5443 25614082 Ten HLA-A*2402 patients were treated with WT1 peptide-pulsed DC vaccination (1 × 10(7) cells) on days 8 and 22 and gemcitabine (1000 mg/m(2) ) on days 1, 8 and 15.
5444 25614082 Patients with liver metastases and high levels of inflammatory markers such as C-reactive protein and interleukin-8 (IL-8) showed poor survival even though a WT1-specific immune response was induced in them.
5445 25617474 HLA-A02:01-restricted epitopes identified from the herpes simplex virus tegument protein VP11/12 preferentially recall polyfunctional effector memory CD8+ T cells from seropositive asymptomatic individuals and protect humanized HLA-A*02:01 transgenic mice against ocular herpes.
5446 25617474 In this study, we used multiple prediction computer-assisted algorithms to identify 10 potential HLA-A*02:01-restricted CD8(+) T cell epitopes from the 718-aa sequence of VP11/12.
5447 25617474 In 10 sequentially studied HLA-A*02:01-positive and HSV-1-seropositive ASYMP individuals, the most frequent, robust, and polyfunctional effector CD8(+) T cell responses, as assessed by a combination of tetramer frequency, granzyme B, granzyme K, perforin, CD107(a/b) cytotoxic degranulation, IFN-γ, and multiplex cytokines assays, were predominantly directed against three epitopes: VP11/1266-74, VP11/12220-228, and VP11/12702-710.
5448 25617474 Interestingly, ASYMP individuals had a significantly higher proportion of CD45RA(low)CCR7(low)CD44(high)CD62L(low)CD27(low)CD28(low)CD8(+) effector memory CD8(+) T cells (TEMs) specific to the three epitopes, compared with symptomatic individuals (with a history of numerous episodes of recurrent ocular herpetic disease).
5449 25617474 Moreover, immunization of HLA-A*02:01 transgenic mice with the three ASYMP CD8(+) TEM cell epitopes induced robust and polyfunctional epitope-specific CD8(+) TEM cells that were associated with a strong protective immunity against ocular herpes infection and disease.
5450 25617474 HLA-A02:01-restricted epitopes identified from the herpes simplex virus tegument protein VP11/12 preferentially recall polyfunctional effector memory CD8+ T cells from seropositive asymptomatic individuals and protect humanized HLA-A*02:01 transgenic mice against ocular herpes.
5451 25617474 In this study, we used multiple prediction computer-assisted algorithms to identify 10 potential HLA-A*02:01-restricted CD8(+) T cell epitopes from the 718-aa sequence of VP11/12.
5452 25617474 In 10 sequentially studied HLA-A*02:01-positive and HSV-1-seropositive ASYMP individuals, the most frequent, robust, and polyfunctional effector CD8(+) T cell responses, as assessed by a combination of tetramer frequency, granzyme B, granzyme K, perforin, CD107(a/b) cytotoxic degranulation, IFN-γ, and multiplex cytokines assays, were predominantly directed against three epitopes: VP11/1266-74, VP11/12220-228, and VP11/12702-710.
5453 25617474 Interestingly, ASYMP individuals had a significantly higher proportion of CD45RA(low)CCR7(low)CD44(high)CD62L(low)CD27(low)CD28(low)CD8(+) effector memory CD8(+) T cells (TEMs) specific to the three epitopes, compared with symptomatic individuals (with a history of numerous episodes of recurrent ocular herpetic disease).
5454 25617474 Moreover, immunization of HLA-A*02:01 transgenic mice with the three ASYMP CD8(+) TEM cell epitopes induced robust and polyfunctional epitope-specific CD8(+) TEM cells that were associated with a strong protective immunity against ocular herpes infection and disease.
5455 25617474 HLA-A02:01-restricted epitopes identified from the herpes simplex virus tegument protein VP11/12 preferentially recall polyfunctional effector memory CD8+ T cells from seropositive asymptomatic individuals and protect humanized HLA-A*02:01 transgenic mice against ocular herpes.
5456 25617474 In this study, we used multiple prediction computer-assisted algorithms to identify 10 potential HLA-A*02:01-restricted CD8(+) T cell epitopes from the 718-aa sequence of VP11/12.
5457 25617474 In 10 sequentially studied HLA-A*02:01-positive and HSV-1-seropositive ASYMP individuals, the most frequent, robust, and polyfunctional effector CD8(+) T cell responses, as assessed by a combination of tetramer frequency, granzyme B, granzyme K, perforin, CD107(a/b) cytotoxic degranulation, IFN-γ, and multiplex cytokines assays, were predominantly directed against three epitopes: VP11/1266-74, VP11/12220-228, and VP11/12702-710.
5458 25617474 Interestingly, ASYMP individuals had a significantly higher proportion of CD45RA(low)CCR7(low)CD44(high)CD62L(low)CD27(low)CD28(low)CD8(+) effector memory CD8(+) T cells (TEMs) specific to the three epitopes, compared with symptomatic individuals (with a history of numerous episodes of recurrent ocular herpetic disease).
5459 25617474 Moreover, immunization of HLA-A*02:01 transgenic mice with the three ASYMP CD8(+) TEM cell epitopes induced robust and polyfunctional epitope-specific CD8(+) TEM cells that were associated with a strong protective immunity against ocular herpes infection and disease.
5460 25617474 HLA-A02:01-restricted epitopes identified from the herpes simplex virus tegument protein VP11/12 preferentially recall polyfunctional effector memory CD8+ T cells from seropositive asymptomatic individuals and protect humanized HLA-A*02:01 transgenic mice against ocular herpes.
5461 25617474 In this study, we used multiple prediction computer-assisted algorithms to identify 10 potential HLA-A*02:01-restricted CD8(+) T cell epitopes from the 718-aa sequence of VP11/12.
5462 25617474 In 10 sequentially studied HLA-A*02:01-positive and HSV-1-seropositive ASYMP individuals, the most frequent, robust, and polyfunctional effector CD8(+) T cell responses, as assessed by a combination of tetramer frequency, granzyme B, granzyme K, perforin, CD107(a/b) cytotoxic degranulation, IFN-γ, and multiplex cytokines assays, were predominantly directed against three epitopes: VP11/1266-74, VP11/12220-228, and VP11/12702-710.
5463 25617474 Interestingly, ASYMP individuals had a significantly higher proportion of CD45RA(low)CCR7(low)CD44(high)CD62L(low)CD27(low)CD28(low)CD8(+) effector memory CD8(+) T cells (TEMs) specific to the three epitopes, compared with symptomatic individuals (with a history of numerous episodes of recurrent ocular herpetic disease).
5464 25617474 Moreover, immunization of HLA-A*02:01 transgenic mice with the three ASYMP CD8(+) TEM cell epitopes induced robust and polyfunctional epitope-specific CD8(+) TEM cells that were associated with a strong protective immunity against ocular herpes infection and disease.
5465 25622186 The functional maturation of BMDCs was confirmed by cytochemistry assay, FITC-dextran, acid phosphatase (ACP) activity, bio-assay and enzyme linked immunosorbent assay (ELISA).We elucidated that IL-2 up-regulated the expression of key surface markers such as: CD80, CD83, CD86, CD40 and MHC II molecules on BMDCs, down-regulated phagocytosis activity, induced more production of IL-12 and TNF-α secreted by BMDCs.
5466 25629522 The capability of ASPH protein-derived HLA class I and II peptides to generate antigen specific CD4(+) and CD8(+) immune responses is unknown.
5467 25629522 Helper CD4(+) T cells and CD8(+) cytotoxic T lymphocytes (CTLs) were co-incubated with the DCs; T cell activation was evaluated by flow cytometric analysis.
5468 25629522 Immunoinformatics tools were used to predict HLA class I- and class II-restricted ASPH sequences, and the corresponding peptides were synthesized.
5469 25629522 ASPH protein-loaded DCs activated both CD4(+) and CD8(+) T cells contained within the PBMC population derived from HCC patients.
5470 25629522 Furthermore, the predicted HLA class I- and class II-restricted ASPH peptides were significantly immunogenic.
5471 25629522 Both HLA class I- and class II-restricted peptides derived from ASPH induce T cell activation in HCC.
5472 25629522 The capability of ASPH protein-derived HLA class I and II peptides to generate antigen specific CD4(+) and CD8(+) immune responses is unknown.
5473 25629522 Helper CD4(+) T cells and CD8(+) cytotoxic T lymphocytes (CTLs) were co-incubated with the DCs; T cell activation was evaluated by flow cytometric analysis.
5474 25629522 Immunoinformatics tools were used to predict HLA class I- and class II-restricted ASPH sequences, and the corresponding peptides were synthesized.
5475 25629522 ASPH protein-loaded DCs activated both CD4(+) and CD8(+) T cells contained within the PBMC population derived from HCC patients.
5476 25629522 Furthermore, the predicted HLA class I- and class II-restricted ASPH peptides were significantly immunogenic.
5477 25629522 Both HLA class I- and class II-restricted peptides derived from ASPH induce T cell activation in HCC.
5478 25629522 The capability of ASPH protein-derived HLA class I and II peptides to generate antigen specific CD4(+) and CD8(+) immune responses is unknown.
5479 25629522 Helper CD4(+) T cells and CD8(+) cytotoxic T lymphocytes (CTLs) were co-incubated with the DCs; T cell activation was evaluated by flow cytometric analysis.
5480 25629522 Immunoinformatics tools were used to predict HLA class I- and class II-restricted ASPH sequences, and the corresponding peptides were synthesized.
5481 25629522 ASPH protein-loaded DCs activated both CD4(+) and CD8(+) T cells contained within the PBMC population derived from HCC patients.
5482 25629522 Furthermore, the predicted HLA class I- and class II-restricted ASPH peptides were significantly immunogenic.
5483 25629522 Both HLA class I- and class II-restricted peptides derived from ASPH induce T cell activation in HCC.
5484 25629522 The capability of ASPH protein-derived HLA class I and II peptides to generate antigen specific CD4(+) and CD8(+) immune responses is unknown.
5485 25629522 Helper CD4(+) T cells and CD8(+) cytotoxic T lymphocytes (CTLs) were co-incubated with the DCs; T cell activation was evaluated by flow cytometric analysis.
5486 25629522 Immunoinformatics tools were used to predict HLA class I- and class II-restricted ASPH sequences, and the corresponding peptides were synthesized.
5487 25629522 ASPH protein-loaded DCs activated both CD4(+) and CD8(+) T cells contained within the PBMC population derived from HCC patients.
5488 25629522 Furthermore, the predicted HLA class I- and class II-restricted ASPH peptides were significantly immunogenic.
5489 25629522 Both HLA class I- and class II-restricted peptides derived from ASPH induce T cell activation in HCC.
5490 25646416 To investigate the disconnection between observed CD8 T-cell responses and immunity to IAV, we used a Poisson liquid chromatography data-independent acquisition MS method to physically detect PR8/34 (H1N1), X31 (H3N2), and Victoria/75 (H3N2) epitopes bound to HLA-A*02:01 on human epithelial cells following in vitro infection.
5491 25653426 Next, we analyzed parameters of DEC205 (CD205), Clec9A, CD11c, CD11b, and CD40 endocytosis and obtained quantitative measurements of internalization speed, surface turnover, and delivered Ag load.
5492 25653426 In contrast, targeting Ag to CD8(+) or CD8(-) DCs enhanced MHC I or MHC II Ag presentation, respectively.
5493 25658616 A phase I clinical trial of CD1c (BDCA-1)+ dendritic cells pulsed with HLA-A*0201 peptides for immunotherapy of metastatic hormone refractory prostate cancer.
5494 25658616 The vaccine was manufactured by pulsing autologous CD1c BDC, prepared by magnetic bead immunoselection from apheresed peripheral blood mononuclear cells, with a cocktail of HLA-A*0201-restricted peptides (prostate-specific antigen, prostate acid phosphatase, prostate specific membrane antigen, and control influenza peptide) and keyhole limpet hemocyanin.
5495 25658616 A phase I clinical trial of CD1c (BDCA-1)+ dendritic cells pulsed with HLA-A*0201 peptides for immunotherapy of metastatic hormone refractory prostate cancer.
5496 25658616 The vaccine was manufactured by pulsing autologous CD1c BDC, prepared by magnetic bead immunoselection from apheresed peripheral blood mononuclear cells, with a cocktail of HLA-A*0201-restricted peptides (prostate-specific antigen, prostate acid phosphatase, prostate specific membrane antigen, and control influenza peptide) and keyhole limpet hemocyanin.
5497 25688236 Proteasomes play a crucial role in the generation of antigenic peptides for presentation on MHC class I molecules, and thus activation of CD8 T cells, as well as activation of the NF-κB pathway.
5498 25698486 We found that delivery of rPmp18D with VCG was more effective than with CpG+FL in up-regulating the expression of molecules critically involved in T cell activation and differentiation, including MHC II, CD40, CD80, and CD86, activation of TLRs and NLRP3 inflammasome engagement, and secretion of IL-1β and TNF-α but not IL-10 and IL-4. rVCG-Pmp18D-immunized mice elicited more robust antigen-specific IFN-γ, IgA and IgG2c antibody responses compared to CpG+FL-delivered rPmp18D.
5499 25723536 The magnitude of CD8+ T cell responses to beneficial regions, together with viral entropy and HLA class I genotype, explained up to 59% of the variation in viral inhibitory activity, with magnitude of the T cell response making the strongest unique contribution.
5500 25726868 Further studies in human preclinical studies and in vivo studies using HLA class I transgenic mice showed TAA-derived long peptides (TAA-LPs) have the capacity to induce not only promiscuous HLA class II-restricted CD4(+) T helper type 1 cells but also tumor-specific CTLs through a cross-presentation mechanism.
5501 25727233 Thirty-five MAP OMPs are reported with nine-mer peptides showing high binding affinity to major histocompatibility complex (MHC) class I molecules and 28 MAP OMPs with 15-mer peptides of high binding affinity for MHC class II molecules.
5502 25727233 The presence of MHC binding epitopes indicates the potential cell-mediated immune response inducing capacity of these MAP OMPs in infected host.
5503 25727233 Thirty-five MAP OMPs are reported with nine-mer peptides showing high binding affinity to major histocompatibility complex (MHC) class I molecules and 28 MAP OMPs with 15-mer peptides of high binding affinity for MHC class II molecules.
5504 25727233 The presence of MHC binding epitopes indicates the potential cell-mediated immune response inducing capacity of these MAP OMPs in infected host.
5505 25729379 A sufficient role of MHC class I molecules on hepatocytes in anti-plasmodial activity of CD8 (+) T cells in vivo.
5506 25729379 Although CD8(+) T cells are shown to mediate the protective immunity against the liver stages of malaria parasites in mice, whether the direct presentation of malaria antigen by major histocompatibility complex (MHC) class I molecules expressed on the liver of infected host is required for anti-plasmodial activity of CD8(+) T cells is still unknown.
5507 25729379 Presently, there is only one CD8(+) epitope, SYVPSAEQI, derived from the circumsporozoite protein of Plasmodium yoelii (PyCS), that mediates anti-malarial protection and is presented in the context of a K(d) molecule.
5508 25729379 Therefore, to investigate the mode of anti-plasmodial activity of CD8+ T cells, we have previously generated C57BL/6 transgenic (Tg) mice, in which a K(d) molecule is expressed only on hepatocyte (Alb-K(d)) or dendritic cell (DC; CD11c-K(d)), by using albumin promoter or CD11c promoter, respectively.
5509 25729379 From splenocytes collected from CD11c-K(d) Tg mice immunized with a synthetic peptide, SYVPSAEQI, which corresponds to the CD8(+) T-cell epitope of PyCS, emulsified in incomplete Freund's adjuvant , a PyCS-specific CD8(+) T-cell line was generated.
5510 25729379 This PyCS-specific CD8(+)T-cell line was then adoptively transferred into a cohort of either MHC-K(d) Tg or Alb-K(d) Tg mice listed above, as well as wild-type C57BL/6 mice.
5511 25729379 We found that the adoptive transfer of a PyCS-specific CD8(+) T-cell line resulted in a significant inhibition of the parasite burden in the liver of Alb-K(d) Tg, as well as MHC-I-K(d) Tg mice, but not of C57BL/6 mice.
5512 25729379 These results indicate that the K(d) molecule expressed by hepatocytes is sufficient in mediating the anti-plasmodial activity of PyCS-specific CD8(+) T cells in vivo.
5513 25729379 A sufficient role of MHC class I molecules on hepatocytes in anti-plasmodial activity of CD8 (+) T cells in vivo.
5514 25729379 Although CD8(+) T cells are shown to mediate the protective immunity against the liver stages of malaria parasites in mice, whether the direct presentation of malaria antigen by major histocompatibility complex (MHC) class I molecules expressed on the liver of infected host is required for anti-plasmodial activity of CD8(+) T cells is still unknown.
5515 25729379 Presently, there is only one CD8(+) epitope, SYVPSAEQI, derived from the circumsporozoite protein of Plasmodium yoelii (PyCS), that mediates anti-malarial protection and is presented in the context of a K(d) molecule.
5516 25729379 Therefore, to investigate the mode of anti-plasmodial activity of CD8+ T cells, we have previously generated C57BL/6 transgenic (Tg) mice, in which a K(d) molecule is expressed only on hepatocyte (Alb-K(d)) or dendritic cell (DC; CD11c-K(d)), by using albumin promoter or CD11c promoter, respectively.
5517 25729379 From splenocytes collected from CD11c-K(d) Tg mice immunized with a synthetic peptide, SYVPSAEQI, which corresponds to the CD8(+) T-cell epitope of PyCS, emulsified in incomplete Freund's adjuvant , a PyCS-specific CD8(+) T-cell line was generated.
5518 25729379 This PyCS-specific CD8(+)T-cell line was then adoptively transferred into a cohort of either MHC-K(d) Tg or Alb-K(d) Tg mice listed above, as well as wild-type C57BL/6 mice.
5519 25729379 We found that the adoptive transfer of a PyCS-specific CD8(+) T-cell line resulted in a significant inhibition of the parasite burden in the liver of Alb-K(d) Tg, as well as MHC-I-K(d) Tg mice, but not of C57BL/6 mice.
5520 25729379 These results indicate that the K(d) molecule expressed by hepatocytes is sufficient in mediating the anti-plasmodial activity of PyCS-specific CD8(+) T cells in vivo.
5521 25738816 CD4 T cell immune responses such as interferon-γ and tumor necrosis factor-α secretion are necessary for Chlamydia immunity.
5522 25738816 Nine proteins were orthologous T cell antigens between C. trachomatis and C. muridarum and 2 of the nine were Pmps which generated MHC class II binding epitopes at distinct sequences within the proteins.
5523 25739076 Anti-metastatic effects of DNA vaccine encoding single-chain trimer composed of MHC I and vascular endothelial growth factor receptor 2 peptide.
5524 25739076 In the present study, we constructed an SCT-encoding VEGFR2 antigen peptide [aa400-408, also known as kinase insert domain-containing receptor (KDR2)], β2m, and mouse MHC class I heavy chain H-2Db [pcDNA3.1(+)-KDR2-β2m-H-2Db, or SCT-KDR2].
5525 25739076 Taken together, the results showed that VEGFR2-targeted SCT vaccination is an effective modality that can be utilized in anti-angiogenic active immunotherapy for various types of cancer.
5526 25739076 Anti-metastatic effects of DNA vaccine encoding single-chain trimer composed of MHC I and vascular endothelial growth factor receptor 2 peptide.
5527 25739076 In the present study, we constructed an SCT-encoding VEGFR2 antigen peptide [aa400-408, also known as kinase insert domain-containing receptor (KDR2)], β2m, and mouse MHC class I heavy chain H-2Db [pcDNA3.1(+)-KDR2-β2m-H-2Db, or SCT-KDR2].
5528 25739076 Taken together, the results showed that VEGFR2-targeted SCT vaccination is an effective modality that can be utilized in anti-angiogenic active immunotherapy for various types of cancer.
5529 25748337 Upon PFWE treatment, BM-DCs dose-dependently upregulated the expression of CD40, CD80, CD86 and MHC II and increased the production of IL-12, IL-6 and tumor necrosis factor (TNF)-α but not for IL-10, which is mediated by TLR4 signaling pathway, at least partially.
5530 25775390 Furthermore, sRCPS increased the levels of IL-4, IL-2, and IFN-γ in CD4(+)T cells and the level of IFN-γ in CD8(+)T cells.
5531 25775390 In addition, sRCPS enhanced the expression of CD40(+), CD80(+), CD86(+), MHC I and MHC II in dendritic cells (DCs) and upregulated the mRNA levels of MHC I, MHC II. sRCPS downregulated the frequency of CD4(+)CD25(+)Foxp3(+) Treg cells. sRCPS increased both cellular and humoral immune responses by upregulating DC maturation, and suppressing the frequency of Treg cells.
5532 25792524 The vaccines were aimed at activating type I CD4(+)T cells and consisted of tumor cells transfected with genes encoding syngeneic MHC class II and CD80 costimulatory molecules, and lacking the MHC II-associated invariant chain.
5533 25792524 During the course of the vaccine studies, we observed that CD80 not only costimulated naïve T cells, but also bound to PD-L1 and prevented tumor cell-expressed PD-L1 from binding to its receptor PD-1 on activated T cells.
5534 25792524 A soluble form of CD80 (CD80-Fc) had the same effect and sustained IFNγ production by both human and murine PD-1(+) activated T cells in the presence of PD-L1(+) human or mouse tumor cells, respectively.
5535 25792524 In vitro studies with human tumor cells indicated that CD80-Fc was more effective than antibodies to either PD-1 or PD-L1 in sustaining T cell production of IFNγ.
5536 25792524 Studies with human T cells blocked for CD28 and with T cells from CD28 knockout mice demonstrated that CD80-Fc simultaneously inhibited PD-L1/PD-1-mediated immune suppression and delivered costimulatory signals to activated T cells, thereby amplifying T cell activation.
5537 25793777 We aimed to determine the effect of SGI-110 on methylation and expression of the cancer testis antigens (CTAs) NY-ESO-1 and MAGE-A in epithelial ovarian cancer (EOC) cells in vitro and in vivo and to establish the impact of SGI-110 on expression of major histocompatibility (MHC) class I and Intracellular Adhesion Molecule 1 (ICAM-1) on EOC cells, and on recognition of EOC cells by NY-ESO-1-specific CD8+ T-cells.
5538 25793777 We also tested the impact of combined SGI-110 and NY-ESO-1-specific CD8+ T-cells on tumor growth and/or murine survival in a xenograft setting.
5539 25793777 SGI-110 enhanced the expression of MHC I and ICAM-1, and enhanced recognition of EOC cells by NY-ESO-1-specific CD8+ T-cells.
5540 25793777 We aimed to determine the effect of SGI-110 on methylation and expression of the cancer testis antigens (CTAs) NY-ESO-1 and MAGE-A in epithelial ovarian cancer (EOC) cells in vitro and in vivo and to establish the impact of SGI-110 on expression of major histocompatibility (MHC) class I and Intracellular Adhesion Molecule 1 (ICAM-1) on EOC cells, and on recognition of EOC cells by NY-ESO-1-specific CD8+ T-cells.
5541 25793777 We also tested the impact of combined SGI-110 and NY-ESO-1-specific CD8+ T-cells on tumor growth and/or murine survival in a xenograft setting.
5542 25793777 SGI-110 enhanced the expression of MHC I and ICAM-1, and enhanced recognition of EOC cells by NY-ESO-1-specific CD8+ T-cells.
5543 25833403 Spheroplasts (bacterial cell devoid of cell wall) are likely to undergo membrane-membrane fusion, leading to the delivery of their content to the cytosol of antigen-presenting cells, thus facilitating MHC class I antigen processing and presentation.
5544 25847967 Future rational CD8 cytotoxic T-cell-based vaccines may follow, targeting virally induced cancers, other nonviral immunogenic tumors, and potentially even nonimmunogenic tumors whose peptide display can be purposely altered by MHC-binding drugs to stimulate immune attack.
5545 25862971 Moreover, the expression of seven immune-related genes (IFN-I, TNF-α, CRP, IL-8, IgM, MHC I and CD8α) in the intestine, kidney and spleen of Aera treated fish was significantly enhanced, which indicated that a better tissue immune response in grass carp was induced by the SWCNTs-Aera vaccine.
5546 25869226 Xenovaccination with rhCEA resulted in the activation of CD4+ T-cell responses in addition to self-reactive CD8+ T-cells, the development of high-titer antibodies against hCEA, and significant antitumor effects upon challenge with hCEA+ tumor cells.
5547 25869226 The superior activity of rhCEAopt compared with hCEAopt was confirmed in hCEA/HHD double-transgenic mice, where potent CD8+ T-cell responses against specific human HLA A*0201 hCEA epitopes were detected.
5548 25894902 Five conserved high score cytotoxic T lymphocyte (CTL) epitopes restricted to HLA-A*0201-binding peptides within the hemagglutinin (HA) protein of the viruses were chosen, and two HA CTL/HK-1 chimera protein models designed.
5549 25936538 The aim of the present study was to identify human leukemia antigen (HLA)-A*0201-restricted epitopes of EPS8 by using a reverse immunology approach.
5550 25936538 At the same time, the CTLs were able to specifically lyse EPS8-expressing cell lines in an HLA-A*0201-restricted manner.
5551 25936538 The aim of the present study was to identify human leukemia antigen (HLA)-A*0201-restricted epitopes of EPS8 by using a reverse immunology approach.
5552 25936538 At the same time, the CTLs were able to specifically lyse EPS8-expressing cell lines in an HLA-A*0201-restricted manner.
5553 25960935 Molecular mimicry of MAGE-A6 and Mycoplasma penetrans HF-2 epitopes in the induction of antitumor CD8+ T-cell responses.
5554 25960935 A promising vaccine strategy for the treatment of cancer involves the use of vaccines incorporating tumor antigen-derived synthetic peptides that can be coordinately recognized by specific CD4+ and CD8+ T-cells.
5555 25960935 Previously, we reported that a MAGE-A6-derived peptide (MAGE-A6172-187) and its highly-immunogenic and cross-reactive homolog derived from Mycoplasma penetrans HF-2 permease (HF-2216-229) are promiscuously presented by multiple HLA-DR alleles to responder CD4+ T-cells obtained from healthy donors and melanoma patients.
5556 25960935 Here, we investigated whether these same peptides could concomitantly stimulate cross-reactive MAGE-A6-specific CD8+ T-cell responses in vitro using cells isolated from HLA-A*0201 (HLA-A2)+ healthy individuals and patients with melanoma.
5557 25960935 We now show that MAGE-A6172-187 and, even more so, HF-2216-229, induce memory CD8+ T cells that recognize HLA-A2+ MAGE-A6+ tumor target cells.
5558 25960935 The immunogenicity of these peptides was at least partially attributed to their embedded MAGE-A6176-185 and HF-2220-229 "homologous" sequences.
5559 25960935 The functional avidity of HF-2216-229 peptide-primed CD8+ T cells for the MAGE-A6172-187 peptide was more than 100-fold greater than that of CD8+ T cells primed with the corresponding MAGE-A6 peptide.
5560 25960935 Additionally, these 2 peptides were recognized in interferon γ (IFNγ) and granzyme B ELISPOT assays by CD8+ T-cell clones displaying variable T-cell receptor (TCR) Vβ usage.
5561 25960935 These data suggest that the immune cross-reactivity of the MAGE-A6172-187 and HF-2216-229 peptides extends to CD8+ T cells, at least in HLA-A2+ donors, and supports the potential translational utility of these epitopes in clinical vaccine formulations and for immunomonitoring of cancer patients.
5562 25962106 Wogonin also promoted the secretion of calreticulin and high-mobility group protein 1 by tumor cells.
5563 25962106 The dephosphorylation of STAT3 contributed to the decreased expression of B7H1 and MHC class I chain-related protein A, and the enhancement of calreticulin on the cell membrane.
5564 26019274 To achieve this, vaccine Ags need to be targeted to the cytosol of dendritic cells, which can activate CD8 T cells via MHC class I (MHCI).
5565 26019274 Immunization in the presence of TPCS2a significantly increased activation of CD8 T cells compared with immunization without TPCS2a and as measured by CD8 T cell proliferation, production of proinflammatory IFN-γ, TNF-α, and IL-2, and prevention of tumor growth.
5566 26019274 CD4-dependent Ab responses were abrogated in mice immunized with TPCS2a-containing particles, suggesting that photosensitization facilitated a shift from default MHC class II toward MHCI Ag presentation.
5567 26019274 To achieve this, vaccine Ags need to be targeted to the cytosol of dendritic cells, which can activate CD8 T cells via MHC class I (MHCI).
5568 26019274 Immunization in the presence of TPCS2a significantly increased activation of CD8 T cells compared with immunization without TPCS2a and as measured by CD8 T cell proliferation, production of proinflammatory IFN-γ, TNF-α, and IL-2, and prevention of tumor growth.
5569 26019274 CD4-dependent Ab responses were abrogated in mice immunized with TPCS2a-containing particles, suggesting that photosensitization facilitated a shift from default MHC class II toward MHCI Ag presentation.
5570 26020813 Because HLA-B is the most polymorphic human MHC class I molecule and correlates strongly with HIV-1 progression, we determined sequences for its ortholog, Patr-B, in 125 Gombe chimpanzees.
5571 26026288 A pilot study in prostate cancer patients treated with the AE37 Ii-key-HER-2/neu polypeptide vaccine suggests that HLA-A*24 and HLA-DRB1*11 alleles may be prognostic and predictive biomarkers for clinical benefit.
5572 26026288 Herein, we aimed to expand these retrospective analyses by studying the predictive impact of HLA-A*24 and HLA-DRB1*11 alleles, which are expressed at high frequencies among responders in our vaccinated patients, for clinical and immunological responses to AE37 vaccination.
5573 26026288 Our data show an increased OS of patients expressing the HLA-DRB1*11 or HLA-A*24 alleles, or both.
5574 26026288 Preexisting (i.e., before vaccinations with AE37) levels of vaccine-specific IFN-γ immunity and plasma TGF-β, among the HLA-A*24 and/or HLA-DRB1*11 positive patients, were strong indicators for immunological responses to AE37 treatment.
5575 26026288 These data suggest that HLA-DRB1*11 and HLA-A*24 are likely to be predictive factors for immunological and clinical responses to vaccination with AE37, though prospective validation in larger cohorts is needed.
5576 26026288 A pilot study in prostate cancer patients treated with the AE37 Ii-key-HER-2/neu polypeptide vaccine suggests that HLA-A*24 and HLA-DRB1*11 alleles may be prognostic and predictive biomarkers for clinical benefit.
5577 26026288 Herein, we aimed to expand these retrospective analyses by studying the predictive impact of HLA-A*24 and HLA-DRB1*11 alleles, which are expressed at high frequencies among responders in our vaccinated patients, for clinical and immunological responses to AE37 vaccination.
5578 26026288 Our data show an increased OS of patients expressing the HLA-DRB1*11 or HLA-A*24 alleles, or both.
5579 26026288 Preexisting (i.e., before vaccinations with AE37) levels of vaccine-specific IFN-γ immunity and plasma TGF-β, among the HLA-A*24 and/or HLA-DRB1*11 positive patients, were strong indicators for immunological responses to AE37 treatment.
5580 26026288 These data suggest that HLA-DRB1*11 and HLA-A*24 are likely to be predictive factors for immunological and clinical responses to vaccination with AE37, though prospective validation in larger cohorts is needed.
5581 26026288 A pilot study in prostate cancer patients treated with the AE37 Ii-key-HER-2/neu polypeptide vaccine suggests that HLA-A*24 and HLA-DRB1*11 alleles may be prognostic and predictive biomarkers for clinical benefit.
5582 26026288 Herein, we aimed to expand these retrospective analyses by studying the predictive impact of HLA-A*24 and HLA-DRB1*11 alleles, which are expressed at high frequencies among responders in our vaccinated patients, for clinical and immunological responses to AE37 vaccination.
5583 26026288 Our data show an increased OS of patients expressing the HLA-DRB1*11 or HLA-A*24 alleles, or both.
5584 26026288 Preexisting (i.e., before vaccinations with AE37) levels of vaccine-specific IFN-γ immunity and plasma TGF-β, among the HLA-A*24 and/or HLA-DRB1*11 positive patients, were strong indicators for immunological responses to AE37 treatment.
5585 26026288 These data suggest that HLA-DRB1*11 and HLA-A*24 are likely to be predictive factors for immunological and clinical responses to vaccination with AE37, though prospective validation in larger cohorts is needed.
5586 26026288 A pilot study in prostate cancer patients treated with the AE37 Ii-key-HER-2/neu polypeptide vaccine suggests that HLA-A*24 and HLA-DRB1*11 alleles may be prognostic and predictive biomarkers for clinical benefit.
5587 26026288 Herein, we aimed to expand these retrospective analyses by studying the predictive impact of HLA-A*24 and HLA-DRB1*11 alleles, which are expressed at high frequencies among responders in our vaccinated patients, for clinical and immunological responses to AE37 vaccination.
5588 26026288 Our data show an increased OS of patients expressing the HLA-DRB1*11 or HLA-A*24 alleles, or both.
5589 26026288 Preexisting (i.e., before vaccinations with AE37) levels of vaccine-specific IFN-γ immunity and plasma TGF-β, among the HLA-A*24 and/or HLA-DRB1*11 positive patients, were strong indicators for immunological responses to AE37 treatment.
5590 26026288 These data suggest that HLA-DRB1*11 and HLA-A*24 are likely to be predictive factors for immunological and clinical responses to vaccination with AE37, though prospective validation in larger cohorts is needed.
5591 26026288 A pilot study in prostate cancer patients treated with the AE37 Ii-key-HER-2/neu polypeptide vaccine suggests that HLA-A*24 and HLA-DRB1*11 alleles may be prognostic and predictive biomarkers for clinical benefit.
5592 26026288 Herein, we aimed to expand these retrospective analyses by studying the predictive impact of HLA-A*24 and HLA-DRB1*11 alleles, which are expressed at high frequencies among responders in our vaccinated patients, for clinical and immunological responses to AE37 vaccination.
5593 26026288 Our data show an increased OS of patients expressing the HLA-DRB1*11 or HLA-A*24 alleles, or both.
5594 26026288 Preexisting (i.e., before vaccinations with AE37) levels of vaccine-specific IFN-γ immunity and plasma TGF-β, among the HLA-A*24 and/or HLA-DRB1*11 positive patients, were strong indicators for immunological responses to AE37 treatment.
5595 26026288 These data suggest that HLA-DRB1*11 and HLA-A*24 are likely to be predictive factors for immunological and clinical responses to vaccination with AE37, though prospective validation in larger cohorts is needed.
5596 26076666 We first identified an inverse correlation of MYCN expression with CD45 mRNA in 101 NB tumor samples.
5597 26076666 The immune response was mediated by tumor-infiltrating T cells in vivo, which revealed MYCN-specific and MHC class I-restricted lysis of inducible MYCN-expressing NB target cells in vitro.
5598 26090808 Moreover, in vivo administration of GB promoted up-regulation of CD86, MHC class I and MHC class II and production of IL-6, IL-12 and TNF-α in spleen DCs.
5599 26090808 Furthermore, Toll like receptor 4 (TLR4) and myeloid differentiation primary response 88 (MyD88) signaling pathway were essential for DC activation induced by GB.
5600 26090808 In addition, GB strongly prompted the proliferation of ovalbumin (OVA)-specific CD4 and CD8 T cells.
5601 26104661 Antileukemia multifunctionality of CD4(+) T cells genetically engineered by HLA class I-restricted and WT1-specific T-cell receptor gene transfer.
5602 26104661 To develop gene-modified T-cell-based antileukemia adoptive immunotherapy, concomitant administration of CD4(+) and CD8(+) T cells that have been gene modified using identical HLA class I-restricted leukemia antigen-specific T-cell receptor (TCR) gene transfer has not yet been fully investigated.
5603 26104661 Here, using CD4(+) and CD8(+) T cells that had been gene modified with a retroviral vector expressing HLA-A*24:02-restricted and Wilms' tumor 1 (WT1)-specific TCR-α/β genes and siRNAs for endogenous TCRs (WT1-siTCR/CD4(+) T cells and WT1-siTCR/CD8(+) T cells), we examined the utility of this strategy.
5604 26104661 WT1-siTCR/CD4(+) T cells sufficiently recognized leukemia cells in an HLA class I-restricted manner and provided target-specific Th1 help for WT1-siTCR/CD8(+) T cells.
5605 26104661 By using a xenografted mouse model, we found that WT1-siTCR/CD4(+) T cells migrated to leukemia sites and subsequently attracted WT1-siTCR/CD8(+) T cells via chemotaxis.
5606 26104661 Therapy-oriented experiments revealed effective enhancement of leukemia suppression mediated by concomitant administration of WT1-siTCR/CD4(+) T cells and WT1-siTCR/CD8(+) T cells.
5607 26104661 Importantly, this augmented efficacy in the presence of WT1-siTCR/CD4(+) T cells was correlated with longer survival and enhanced formation of memory T cells by WT1-siTCR/CD8(+) T cells.
5608 26104661 Antileukemia multifunctionality of CD4(+) T cells genetically engineered by HLA class I-restricted and WT1-specific T-cell receptor gene transfer.
5609 26104661 To develop gene-modified T-cell-based antileukemia adoptive immunotherapy, concomitant administration of CD4(+) and CD8(+) T cells that have been gene modified using identical HLA class I-restricted leukemia antigen-specific T-cell receptor (TCR) gene transfer has not yet been fully investigated.
5610 26104661 Here, using CD4(+) and CD8(+) T cells that had been gene modified with a retroviral vector expressing HLA-A*24:02-restricted and Wilms' tumor 1 (WT1)-specific TCR-α/β genes and siRNAs for endogenous TCRs (WT1-siTCR/CD4(+) T cells and WT1-siTCR/CD8(+) T cells), we examined the utility of this strategy.
5611 26104661 WT1-siTCR/CD4(+) T cells sufficiently recognized leukemia cells in an HLA class I-restricted manner and provided target-specific Th1 help for WT1-siTCR/CD8(+) T cells.
5612 26104661 By using a xenografted mouse model, we found that WT1-siTCR/CD4(+) T cells migrated to leukemia sites and subsequently attracted WT1-siTCR/CD8(+) T cells via chemotaxis.
5613 26104661 Therapy-oriented experiments revealed effective enhancement of leukemia suppression mediated by concomitant administration of WT1-siTCR/CD4(+) T cells and WT1-siTCR/CD8(+) T cells.
5614 26104661 Importantly, this augmented efficacy in the presence of WT1-siTCR/CD4(+) T cells was correlated with longer survival and enhanced formation of memory T cells by WT1-siTCR/CD8(+) T cells.
5615 26104661 Antileukemia multifunctionality of CD4(+) T cells genetically engineered by HLA class I-restricted and WT1-specific T-cell receptor gene transfer.
5616 26104661 To develop gene-modified T-cell-based antileukemia adoptive immunotherapy, concomitant administration of CD4(+) and CD8(+) T cells that have been gene modified using identical HLA class I-restricted leukemia antigen-specific T-cell receptor (TCR) gene transfer has not yet been fully investigated.
5617 26104661 Here, using CD4(+) and CD8(+) T cells that had been gene modified with a retroviral vector expressing HLA-A*24:02-restricted and Wilms' tumor 1 (WT1)-specific TCR-α/β genes and siRNAs for endogenous TCRs (WT1-siTCR/CD4(+) T cells and WT1-siTCR/CD8(+) T cells), we examined the utility of this strategy.
5618 26104661 WT1-siTCR/CD4(+) T cells sufficiently recognized leukemia cells in an HLA class I-restricted manner and provided target-specific Th1 help for WT1-siTCR/CD8(+) T cells.
5619 26104661 By using a xenografted mouse model, we found that WT1-siTCR/CD4(+) T cells migrated to leukemia sites and subsequently attracted WT1-siTCR/CD8(+) T cells via chemotaxis.
5620 26104661 Therapy-oriented experiments revealed effective enhancement of leukemia suppression mediated by concomitant administration of WT1-siTCR/CD4(+) T cells and WT1-siTCR/CD8(+) T cells.
5621 26104661 Importantly, this augmented efficacy in the presence of WT1-siTCR/CD4(+) T cells was correlated with longer survival and enhanced formation of memory T cells by WT1-siTCR/CD8(+) T cells.
5622 26104661 Antileukemia multifunctionality of CD4(+) T cells genetically engineered by HLA class I-restricted and WT1-specific T-cell receptor gene transfer.
5623 26104661 To develop gene-modified T-cell-based antileukemia adoptive immunotherapy, concomitant administration of CD4(+) and CD8(+) T cells that have been gene modified using identical HLA class I-restricted leukemia antigen-specific T-cell receptor (TCR) gene transfer has not yet been fully investigated.
5624 26104661 Here, using CD4(+) and CD8(+) T cells that had been gene modified with a retroviral vector expressing HLA-A*24:02-restricted and Wilms' tumor 1 (WT1)-specific TCR-α/β genes and siRNAs for endogenous TCRs (WT1-siTCR/CD4(+) T cells and WT1-siTCR/CD8(+) T cells), we examined the utility of this strategy.
5625 26104661 WT1-siTCR/CD4(+) T cells sufficiently recognized leukemia cells in an HLA class I-restricted manner and provided target-specific Th1 help for WT1-siTCR/CD8(+) T cells.
5626 26104661 By using a xenografted mouse model, we found that WT1-siTCR/CD4(+) T cells migrated to leukemia sites and subsequently attracted WT1-siTCR/CD8(+) T cells via chemotaxis.
5627 26104661 Therapy-oriented experiments revealed effective enhancement of leukemia suppression mediated by concomitant administration of WT1-siTCR/CD4(+) T cells and WT1-siTCR/CD8(+) T cells.
5628 26104661 Importantly, this augmented efficacy in the presence of WT1-siTCR/CD4(+) T cells was correlated with longer survival and enhanced formation of memory T cells by WT1-siTCR/CD8(+) T cells.
5629 26191056 Low VL (<10,000 copies/ml) and HLA-A*74:01 were the main predictors of CD4:CD8 ratio >1.0, but HLA variants (e.g., HLA-B*57 and HLA-B*81) previously associated with VL and/or CD4 trajectories in eastern and southern Africans had no obvious impact on CD4:CD8 ratio.
5630 26214521 Effective cancer vaccines deliver concentrated antigen to both HLA class I and II molecules of DCs, promoting both CD4 and CD8 T cell responses.
5631 26214521 Drugs or physical treatments can mitigate the immunosuppressive cancer microenvironment and include chemotherapeutics, radiation, indoleamine 2,3-dioxygenase (IDO) inhibitors, inhibitors of T cell checkpoints, agonists of selected TNF receptor family members, and inhibitors of undesirable cytokines.
5632 26232860 Transcriptional analysis showed that vaccination with rTAT-Sia10 up-regulated the expression of the genes encoding IL-1β, IL-8, NKEF, Mx, IgD, IgM, TNFα, MHC I α, MHC IIα, and CD8α.
5633 26283480 YFV induced an increased functional responsiveness to IL-12 and IL-18, as well as to K562 cells, indicating that the NK cells were primed in vivo.
5634 26283480 The NK cell responses were associated primarily with the stage of differentiation, because the magnitude of induced Ki67 and CD69 expression was distinctly higher in CD57(-) NK cells.
5635 26283480 Taken together, our results indicate that NK cells are primed by type I/III IFN in vivo early after YFV infection and that their response is governed primarily by the differentiation stage, independently of killer cell Ig-like receptor/HLA class I-mediated inhibition or education.
5636 26284472 NKG2D ligands (NKG2DLs) are a group of stress-inducible major histocompatibility complex (MHC) class I-like molecules that act as a danger signal alerting the immune system to the presence of abnormal cells.
5637 26284472 Some mammals have a third family of NKG2DL-like class I genes which we named MILL (MHC class I-like located near the leukocyte receptor complex).
5638 26284472 NKG2D ligands (NKG2DLs) are a group of stress-inducible major histocompatibility complex (MHC) class I-like molecules that act as a danger signal alerting the immune system to the presence of abnormal cells.
5639 26284472 Some mammals have a third family of NKG2DL-like class I genes which we named MILL (MHC class I-like located near the leukocyte receptor complex).
5640 26296422 Host defense against viruses and intracellular parasites depends on effector CD8(+) T cells, whose optimal clonal expansion, differentiation, and memory properties require signals from CD4(+) T cells.
5641 26296422 Surprisingly, initial priming of CD4(+) and CD8(+) T cells was spatially segregated within the lymph node and occurred on different DCs with temporally distinct patterns of antigen presentation via MHCI versus MHCII molecules.
5642 26296422 DCs that co-present antigen via both MHC molecules were detected at a later stage; these XCR1(+) DCs are the critical platform involved in CD4(+) T cell augmentation of CD8(+) T cell responses.
5643 26331453 The present study attempted to identify T helper epitope long peptides capable of inducing cytotoxic T lymphocytes (CTL) from Lck antigen (p56(Lck) ), the src family tyrosine kinase, which is known to be aberrantly expressed in metastatic cancers cells, in order to develop a long peptide-based cancer vaccine for HLA-A2(+) cancer patients.
5644 26331453 These peptides were screened for their reactivity to immunoglobulin G (IgG) from plasma of cancer patients, followed by testing of their ability to induce both CD4(+) and CD8(+) T lymphocytes showing not only peptide-specific IFN-γ production but cytotoxicity against HLA-A2(+) cancer cells from peripheral blood mononuclear cells (PBMC) of HLA-A2(+) cancer patients.
5645 26331453 Among 94 peptides tested, the three T helper epitope long peptides and their inner CTL epitope short peptides with HLA-A2 binding motifs were frequently recognized by IgG of cancer patients, and efficiently induced both CD4(+) IFN-γ(+) and CD8(+) IFN-γ(+) T lymphocytes.
5646 26331453 Patients' PBMC stimulated with these long peptides showed cytotoxicity against HLA-A2(+) Lck(+) cancer cells in HLA-class I and HLA-class II dependent manners.
5647 26375851 In the overall dataset, the total number of unique self-peptides eluted from HLA-B molecules was larger than from HLA-A molecules, and they were derived from a larger number of source proteins.
5648 26375851 These results in B cells suggest that HLA-B molecules possibly present a more diverse repertoire compared to their HLA-A counterparts, which may contribute to their immunodominance.
5649 26375851 In the overall dataset, the total number of unique self-peptides eluted from HLA-B molecules was larger than from HLA-A molecules, and they were derived from a larger number of source proteins.
5650 26375851 These results in B cells suggest that HLA-B molecules possibly present a more diverse repertoire compared to their HLA-A counterparts, which may contribute to their immunodominance.
5651 26381649 Inferring Protective CD8+ T-Cell Epitopes for NS5 Protein of Four Serotypes of Dengue Virus Chinese Isolates Based on HLA-A, -B and -C Allelic Distribution: Implications for Epitope-Based Universal Vaccine Design.
5652 26381649 The most highly conserved flavivirus protein, NS5, is an indispensable target of CD8+ T-cells, making it an ideal vaccine design target.
5653 26381649 Using the Immune Epitope Database (IEDB), CD8+ T-cell epitopes of the dengue virus (DENV) NS5 protein were predicted by genotypic frequency of the HLA-A,-B, and-C alleles in Chinese population.
5654 26381649 Inferring Protective CD8+ T-Cell Epitopes for NS5 Protein of Four Serotypes of Dengue Virus Chinese Isolates Based on HLA-A, -B and -C Allelic Distribution: Implications for Epitope-Based Universal Vaccine Design.
5655 26381649 The most highly conserved flavivirus protein, NS5, is an indispensable target of CD8+ T-cells, making it an ideal vaccine design target.
5656 26381649 Using the Immune Epitope Database (IEDB), CD8+ T-cell epitopes of the dengue virus (DENV) NS5 protein were predicted by genotypic frequency of the HLA-A,-B, and-C alleles in Chinese population.
5657 26395101 In response to microbial pattern molecules, these DCs upgrade the maturation stage sufficient to improve cross-presentation of exogenous Ag, and upregulation of MHC and costimulators, allowing CD4/CD8 T cells to proliferate and liberating cytokines/chemokines that support lymphocyte attraction and survival.
5658 26395101 Mouse CD8α(+) DCs express TLR7 and TLR9 in addition to the TLR2 family (TLR1, 2, and 6) and TLR3, whereas human CD141(+) DCs exclusively express the TLR2 family and TLR3.
5659 26395101 In contrast, TLR2 and TLR3 are similarly expressed in both human and mouse Ag-presenting DCs.
5660 26395101 Bacillus Calmette-Guerin peptidoglycan and polyinosinic-polycytidylic acid are representative agonists for TLR2 and TLR3, respectively, although they additionally stimulate cytoplasmic sensors: their functional specificities may not be limited to the relevant TLRs.
5661 26395101 We herein summarize the history and perspectives of TLR2 and TLR3 agonists in vaccine-adjuvant immunotherapy for cancer.
5662 26398429 Taking advantage of the high homology between mouse and human TERT, we investigated immunogenicity and antitumor efficiency of the liposomal TERT peptides in HLA-A*0201 transgenic HHD mice.
5663 26405584 To generate tumor-specific immune response, a novel cancer vaccine was formulated in DepoVax platform (DPX-Survivac) using survivin HLA class I peptides.
5664 26405584 Strong T cell responses were associated with differentiation of naïve T cells into central/effector memory (CM/EM) and late differentiated (LD) polyfunctional antigen-specific CD4+ and CD8+ T cells.
5665 26416257 Binding register prediction is concerned with determining the minimal core region of nine residues directly in contact with the MHC binding cleft, a crucial piece of information both for the identification and design of CD4(+) T cell antigens.
5666 26422112 The impact of HLA class I and EBV latency-II antigen-specific CD8(+) T cells on the pathogenesis of EBV(+) Hodgkin lymphoma.
5667 26422112 Interestingly, CD8 and LMP2A expression were correlated strongly and, for a given LMP2A level, CD8 was elevated markedly in HLA-A*02(-) versus HLA-A*02(+) EBV(+) cHL patients, suggesting that LMP2A-specific CD8(+) T cell anti-tumoral immunity may be relatively ineffective in HLA-A*02(-) EBV(+) cHL.
5668 26422112 In newly diagnosed EBV(+) cHL, the magnitude of ex-vivo LMP1/2A-specific CD8(+) T cell responses was elevated in HLA-A*02(+) patients.
5669 26422112 Furthermore, in a controlled in-vitro assay, LMP2A-specific CD8(+) T cells from healthy HLA-A*02 heterozygotes expanded to a greater extent with HLA-A*02-restricted compared to non-HLA-A*02-restricted cell lines.
5670 26422112 In an extensive analysis of HLA class I-restricted immunity, immunodominant EBNA3A/3B/3C-specific CD8(+) T cell responses were stimulated by numerous HLA class I molecules, whereas the subdominant LMP1/2A-specific responses were confined largely to HLA-A*02.
5671 26422112 Our results demonstrate that HLA-A*02 mediates a modest, but none the less stronger, EBV-specific CD8(+) T cell response than non-HLA-A*02 alleles, an effect confined to EBV latency-II antigens.
5672 26422112 Thus, the protective effect of HLA-A*02 against EBV(+) cHL is not a surrogate association, but reflects the impact of HLA class I on EBV latency-II antigen-specific CD8(+) T cell hierarchies.
5673 26422112 The impact of HLA class I and EBV latency-II antigen-specific CD8(+) T cells on the pathogenesis of EBV(+) Hodgkin lymphoma.
5674 26422112 Interestingly, CD8 and LMP2A expression were correlated strongly and, for a given LMP2A level, CD8 was elevated markedly in HLA-A*02(-) versus HLA-A*02(+) EBV(+) cHL patients, suggesting that LMP2A-specific CD8(+) T cell anti-tumoral immunity may be relatively ineffective in HLA-A*02(-) EBV(+) cHL.
5675 26422112 In newly diagnosed EBV(+) cHL, the magnitude of ex-vivo LMP1/2A-specific CD8(+) T cell responses was elevated in HLA-A*02(+) patients.
5676 26422112 Furthermore, in a controlled in-vitro assay, LMP2A-specific CD8(+) T cells from healthy HLA-A*02 heterozygotes expanded to a greater extent with HLA-A*02-restricted compared to non-HLA-A*02-restricted cell lines.
5677 26422112 In an extensive analysis of HLA class I-restricted immunity, immunodominant EBNA3A/3B/3C-specific CD8(+) T cell responses were stimulated by numerous HLA class I molecules, whereas the subdominant LMP1/2A-specific responses were confined largely to HLA-A*02.
5678 26422112 Our results demonstrate that HLA-A*02 mediates a modest, but none the less stronger, EBV-specific CD8(+) T cell response than non-HLA-A*02 alleles, an effect confined to EBV latency-II antigens.
5679 26422112 Thus, the protective effect of HLA-A*02 against EBV(+) cHL is not a surrogate association, but reflects the impact of HLA class I on EBV latency-II antigen-specific CD8(+) T cell hierarchies.
5680 26422112 The impact of HLA class I and EBV latency-II antigen-specific CD8(+) T cells on the pathogenesis of EBV(+) Hodgkin lymphoma.
5681 26422112 Interestingly, CD8 and LMP2A expression were correlated strongly and, for a given LMP2A level, CD8 was elevated markedly in HLA-A*02(-) versus HLA-A*02(+) EBV(+) cHL patients, suggesting that LMP2A-specific CD8(+) T cell anti-tumoral immunity may be relatively ineffective in HLA-A*02(-) EBV(+) cHL.
5682 26422112 In newly diagnosed EBV(+) cHL, the magnitude of ex-vivo LMP1/2A-specific CD8(+) T cell responses was elevated in HLA-A*02(+) patients.
5683 26422112 Furthermore, in a controlled in-vitro assay, LMP2A-specific CD8(+) T cells from healthy HLA-A*02 heterozygotes expanded to a greater extent with HLA-A*02-restricted compared to non-HLA-A*02-restricted cell lines.
5684 26422112 In an extensive analysis of HLA class I-restricted immunity, immunodominant EBNA3A/3B/3C-specific CD8(+) T cell responses were stimulated by numerous HLA class I molecules, whereas the subdominant LMP1/2A-specific responses were confined largely to HLA-A*02.
5685 26422112 Our results demonstrate that HLA-A*02 mediates a modest, but none the less stronger, EBV-specific CD8(+) T cell response than non-HLA-A*02 alleles, an effect confined to EBV latency-II antigens.
5686 26422112 Thus, the protective effect of HLA-A*02 against EBV(+) cHL is not a surrogate association, but reflects the impact of HLA class I on EBV latency-II antigen-specific CD8(+) T cell hierarchies.
5687 26422112 The impact of HLA class I and EBV latency-II antigen-specific CD8(+) T cells on the pathogenesis of EBV(+) Hodgkin lymphoma.
5688 26422112 Interestingly, CD8 and LMP2A expression were correlated strongly and, for a given LMP2A level, CD8 was elevated markedly in HLA-A*02(-) versus HLA-A*02(+) EBV(+) cHL patients, suggesting that LMP2A-specific CD8(+) T cell anti-tumoral immunity may be relatively ineffective in HLA-A*02(-) EBV(+) cHL.
5689 26422112 In newly diagnosed EBV(+) cHL, the magnitude of ex-vivo LMP1/2A-specific CD8(+) T cell responses was elevated in HLA-A*02(+) patients.
5690 26422112 Furthermore, in a controlled in-vitro assay, LMP2A-specific CD8(+) T cells from healthy HLA-A*02 heterozygotes expanded to a greater extent with HLA-A*02-restricted compared to non-HLA-A*02-restricted cell lines.
5691 26422112 In an extensive analysis of HLA class I-restricted immunity, immunodominant EBNA3A/3B/3C-specific CD8(+) T cell responses were stimulated by numerous HLA class I molecules, whereas the subdominant LMP1/2A-specific responses were confined largely to HLA-A*02.
5692 26422112 Our results demonstrate that HLA-A*02 mediates a modest, but none the less stronger, EBV-specific CD8(+) T cell response than non-HLA-A*02 alleles, an effect confined to EBV latency-II antigens.
5693 26422112 Thus, the protective effect of HLA-A*02 against EBV(+) cHL is not a surrogate association, but reflects the impact of HLA class I on EBV latency-II antigen-specific CD8(+) T cell hierarchies.
5694 26422112 The impact of HLA class I and EBV latency-II antigen-specific CD8(+) T cells on the pathogenesis of EBV(+) Hodgkin lymphoma.
5695 26422112 Interestingly, CD8 and LMP2A expression were correlated strongly and, for a given LMP2A level, CD8 was elevated markedly in HLA-A*02(-) versus HLA-A*02(+) EBV(+) cHL patients, suggesting that LMP2A-specific CD8(+) T cell anti-tumoral immunity may be relatively ineffective in HLA-A*02(-) EBV(+) cHL.
5696 26422112 In newly diagnosed EBV(+) cHL, the magnitude of ex-vivo LMP1/2A-specific CD8(+) T cell responses was elevated in HLA-A*02(+) patients.
5697 26422112 Furthermore, in a controlled in-vitro assay, LMP2A-specific CD8(+) T cells from healthy HLA-A*02 heterozygotes expanded to a greater extent with HLA-A*02-restricted compared to non-HLA-A*02-restricted cell lines.
5698 26422112 In an extensive analysis of HLA class I-restricted immunity, immunodominant EBNA3A/3B/3C-specific CD8(+) T cell responses were stimulated by numerous HLA class I molecules, whereas the subdominant LMP1/2A-specific responses were confined largely to HLA-A*02.
5699 26422112 Our results demonstrate that HLA-A*02 mediates a modest, but none the less stronger, EBV-specific CD8(+) T cell response than non-HLA-A*02 alleles, an effect confined to EBV latency-II antigens.
5700 26422112 Thus, the protective effect of HLA-A*02 against EBV(+) cHL is not a surrogate association, but reflects the impact of HLA class I on EBV latency-II antigen-specific CD8(+) T cell hierarchies.
5701 26422112 The impact of HLA class I and EBV latency-II antigen-specific CD8(+) T cells on the pathogenesis of EBV(+) Hodgkin lymphoma.
5702 26422112 Interestingly, CD8 and LMP2A expression were correlated strongly and, for a given LMP2A level, CD8 was elevated markedly in HLA-A*02(-) versus HLA-A*02(+) EBV(+) cHL patients, suggesting that LMP2A-specific CD8(+) T cell anti-tumoral immunity may be relatively ineffective in HLA-A*02(-) EBV(+) cHL.
5703 26422112 In newly diagnosed EBV(+) cHL, the magnitude of ex-vivo LMP1/2A-specific CD8(+) T cell responses was elevated in HLA-A*02(+) patients.
5704 26422112 Furthermore, in a controlled in-vitro assay, LMP2A-specific CD8(+) T cells from healthy HLA-A*02 heterozygotes expanded to a greater extent with HLA-A*02-restricted compared to non-HLA-A*02-restricted cell lines.
5705 26422112 In an extensive analysis of HLA class I-restricted immunity, immunodominant EBNA3A/3B/3C-specific CD8(+) T cell responses were stimulated by numerous HLA class I molecules, whereas the subdominant LMP1/2A-specific responses were confined largely to HLA-A*02.
5706 26422112 Our results demonstrate that HLA-A*02 mediates a modest, but none the less stronger, EBV-specific CD8(+) T cell response than non-HLA-A*02 alleles, an effect confined to EBV latency-II antigens.
5707 26422112 Thus, the protective effect of HLA-A*02 against EBV(+) cHL is not a surrogate association, but reflects the impact of HLA class I on EBV latency-II antigen-specific CD8(+) T cell hierarchies.
5708 26422112 The impact of HLA class I and EBV latency-II antigen-specific CD8(+) T cells on the pathogenesis of EBV(+) Hodgkin lymphoma.
5709 26422112 Interestingly, CD8 and LMP2A expression were correlated strongly and, for a given LMP2A level, CD8 was elevated markedly in HLA-A*02(-) versus HLA-A*02(+) EBV(+) cHL patients, suggesting that LMP2A-specific CD8(+) T cell anti-tumoral immunity may be relatively ineffective in HLA-A*02(-) EBV(+) cHL.
5710 26422112 In newly diagnosed EBV(+) cHL, the magnitude of ex-vivo LMP1/2A-specific CD8(+) T cell responses was elevated in HLA-A*02(+) patients.
5711 26422112 Furthermore, in a controlled in-vitro assay, LMP2A-specific CD8(+) T cells from healthy HLA-A*02 heterozygotes expanded to a greater extent with HLA-A*02-restricted compared to non-HLA-A*02-restricted cell lines.
5712 26422112 In an extensive analysis of HLA class I-restricted immunity, immunodominant EBNA3A/3B/3C-specific CD8(+) T cell responses were stimulated by numerous HLA class I molecules, whereas the subdominant LMP1/2A-specific responses were confined largely to HLA-A*02.
5713 26422112 Our results demonstrate that HLA-A*02 mediates a modest, but none the less stronger, EBV-specific CD8(+) T cell response than non-HLA-A*02 alleles, an effect confined to EBV latency-II antigens.
5714 26422112 Thus, the protective effect of HLA-A*02 against EBV(+) cHL is not a surrogate association, but reflects the impact of HLA class I on EBV latency-II antigen-specific CD8(+) T cell hierarchies.
5715 26437244 We report the structures of two TCRs, derived from human induced T regulatory (iT(reg)) cells, complexed to an MHC class II molecule presenting a proinsulin-derived peptide.
5716 26439698 PPE26 functionally stimulates macrophage activation by augmenting pro-inflammatory cytokine production (TNF-α, IL-6 and IL-12 p40) and the expression of cell surface markers (CD80, CD86, MHC class I and II).
5717 26439698 We observed that PPE26-treated macrophages effectively polarizes naïve CD4(+) T cells to up-regulate CXCR3 expression, and to secrete IFN-γ and IL-2, indicating PPE26 contributes to the Th1 polarization during the immune response.
5718 26439698 Moreover, PPE26 effectively induces the reciprocal expansion of effector/memory CD4(+)/CD8(+) CD44(high)CD62L(low) T cells in the spleens of mice immunized with this strain.
5719 26439909 Interaction of a dengue virus NS1-derived peptide with the inhibitory receptor KIR3DL1 on natural killer cells.
5720 26439909 Killer immunoglobulin-like receptors (KIRs) interact with human leucocyte antigen (HLA) class I ligands and play a key role in the regulation and activation of NK cells.
5721 26439909 During our investigation of CD8(+) T cell responses to a conserved HLA-B57-restricted epitope derived from dengue virus (DENV) non-structural protein-1 (NS1), we observed substantial binding of the tetrameric complex to non-T/non-B lymphocytes in peripheral blood mononuclear cells (PBMC) from a long-standing clinical cohort in Thailand.
5722 26439909 We confirmed binding of the NS1 tetramer to CD56(dim) NK cells, which are known to express KIRs.
5723 26439909 Using depletion studies and KIR-transfected cell lines, we demonstrated further that the NS1 tetramer bound the inhibitory receptor KIR3DL1.
5724 26442104 IDO and RhoC, both important in human cancer development and progression, were used as vaccine targets and 12 pigs were immunized with overlapping 20mer peptides spanning the entire porcine IDO and RhoC sequences formulated in CTL-inducing adjuvants: CAF09, CASAC, Montanide ISA 51 VG, or PBS.
5725 26442104 Taking advantage of recombinant swine MHC class I molecules (SLAs), the peptide-SLA complex stability was measured for 198 IDO- or RhoC-derived 9-11mer peptides predicted to bind to SLA-1(*)04:01, -1(*)07:02, -2(*)04:01, -2(*)05:02, and/or -3(*)04:01.
5726 26442104 By IFN-γ release in PBMC cultures we monitored the vaccine-induced peptide-specific CTL responses, and found responses to both IDO- and RhoC-derived peptides across all groups with no adjuvant being superior.
5727 26453454 HLA-DR is the most commonly expressed and likely the most medically important human MHC class II, antigen presenting protein.
5728 26453750 Human cells expressing HLA class I ligands for inhibitory receptors KIR2DL1, KIR2DL2/3, or CD94-NKG2A were transfected with IL-15Rα.
5729 26453750 Proliferation of primary NK cells in response to transpresented IL-15 was reduced by engagement of either KIR2DL1 or KIR2DL2/3 by cognate HLA-C ligands.
5730 26453750 Inhibitory KIR-HLA-C interactions did not reduce the proliferation induced by soluble IL-15.
5731 26453750 Therefore, transpresentation of IL-15 is subject to downregulation by MHC class I-specific inhibitory receptors.
5732 26453750 Similarly, proliferation of the NKG2A(+) cell line NKL induced by IL-15 transpresentation was inhibited by HLA-E.
5733 26453750 Coengagement of inhibitory receptors, either KIR2DL1 or CD94-NKG2A, did not inhibit phosphorylation of Stat5 but inhibited selectively phosphorylation of Akt and S6 ribosomal protein.
5734 26453750 Human cells expressing HLA class I ligands for inhibitory receptors KIR2DL1, KIR2DL2/3, or CD94-NKG2A were transfected with IL-15Rα.
5735 26453750 Proliferation of primary NK cells in response to transpresented IL-15 was reduced by engagement of either KIR2DL1 or KIR2DL2/3 by cognate HLA-C ligands.
5736 26453750 Inhibitory KIR-HLA-C interactions did not reduce the proliferation induced by soluble IL-15.
5737 26453750 Therefore, transpresentation of IL-15 is subject to downregulation by MHC class I-specific inhibitory receptors.
5738 26453750 Similarly, proliferation of the NKG2A(+) cell line NKL induced by IL-15 transpresentation was inhibited by HLA-E.
5739 26453750 Coengagement of inhibitory receptors, either KIR2DL1 or CD94-NKG2A, did not inhibit phosphorylation of Stat5 but inhibited selectively phosphorylation of Akt and S6 ribosomal protein.
5740 26467324 We here report for the first time the identification of 75 HIV-1-derived peptides bound to HLA class I complexes that were purified directly from HIV-1-infected human primary CD4(+) T cells and the C8166 human T-cell line.
5741 20432235 HLA-A 0201-restricted virus-specific CD8(+) CTL do not appear to control HIV effectively in vivo.