0 3 The the DT 4 10 tumour tumour NN 11 21 associated associated JJ 22 26 cell cell NN 27 34 surface surface NN 35 42 antigen antigen NN 43 46 A6H a6h NN 47 49 is be VBZ 50 63 costimulatory costimulatory JJ 64 67 for for IN 68 73 human human JJ 74 78 CD4+ cd4+ JJ 79 82 but but CC 83 86 not not RB 87 91 CD8+ cd8+ JJ 92 93 T t NN 94 99 cells cell NNS 99 100 . . . 102 105 The the DT 106 109 A6H A6H NNP 110 120 monoclonal monoclonal JJ 121 129 antibody antibody NN 130 131 ( ( ( 131 134 mAb mab NN 134 135 ) ) ) 136 146 recognizes recognize VBZ 147 148 a a DT 149 164 120,000-140,000 120,000-140,000 CD 165 167 MW MW NNP 168 175 antigen antigen NN 176 180 that that WDT 181 183 is be VBZ 184 193 expressed express VBN 194 196 at at IN 197 204 similar similar JJ 205 214 densities density NNS 215 217 on on IN 218 223 85-90 85-90 CD 223 224 % % NN 225 227 of of IN 228 233 human human JJ 234 238 CD4+ cd4+ JJ 239 242 and and CC 243 247 CD8+ cd8+ JJ 248 249 T t NN 250 255 cells cell NNS 256 259 and and CC 260 262 on on IN 263 268 renal renal JJ 269 273 cell cell NN 274 284 carcinomas carcinoma NNS 284 285 . . . 286 289 The the DT 290 297 binding binding NN 298 300 of of IN 301 304 the the DT 305 308 A6H A6H NNP 309 312 mAb mab NN 313 320 induced induce VBD 321 322 a a DT 323 336 costimulatory costimulatory JJ 337 343 signal signal NN 344 346 in in IN 347 355 anti-CD3 anti-cd3 JJ 356 365 activated activate VBN 366 367 T t NN 368 373 cells cell NNS 373 374 . . . 375 377 In in IN 378 381 the the DT 382 389 present present JJ 390 396 report report NN 396 397 , , , 398 400 we we PRP 401 405 show show VBP 406 410 that that IN 411 414 A6H a6h NN 415 427 costimulated costimulate VBD 428 432 cell cell NN 433 446 proliferation proliferation NN 447 450 and and CC 451 459 cytokine cytokine NN 460 470 production production NN 471 473 in in IN 474 482 purified purify VBN 483 487 CD4+ cd4+ JJ 488 489 T t NN 490 495 cells cell NNS 495 496 . . . 497 509 Unexpectedly unexpectedly RB 509 510 , , , 511 514 the the DT 515 519 CD8+ cd8+ JJ 520 526 T-cell T-cell NNP 527 540 subpopulation subpopulation NN 541 547 failed fail VBD 548 550 to to TO 551 558 respond respond VB 558 559 . . . 560 564 CD4+ cd4+ JJ 565 566 T t NN 567 572 cells cell NNS 573 585 costimulated costimulate VBN 586 590 with with IN 591 594 the the DT 595 598 A6H A6H NNP 599 602 mAb mab NN 603 614 upregulated upregulate VBD 615 619 CD80 cd80 NN 619 620 , , , 621 625 CD86 CD86 NNP 625 626 , , , 627 631 CD71 CD71 NNP 631 632 , , , 633 646 interleukin-2 interleukin-2 NN 647 648 ( ( ( 648 654 IL-2)R IL-2)R NNP 655 660 alpha alpha NN 660 661 , , , 662 667 IL-2R IL-2R NNP 668 672 beta beta NN 673 676 and and CC 677 682 IL-2R il-2r NN 683 688 gamma gamma NN 688 689 , , , 690 695 while while IN 696 698 no no DT 699 712 corresponding corresponding JJ 713 726 up-regulation up-regulation NN 727 729 of of IN 730 735 these these DT 736 740 cell cell NN 741 748 surface surface NN 749 758 molecules molecule NNS 759 762 was be VBD 763 767 seen see VBN 768 770 in in IN 771 775 CD8+ cd8+ JJ 776 777 T t NN 778 783 cells cell NNS 783 784 . . . 785 787 In in IN 788 793 order order NN 794 796 to to TO 797 808 investigate investigate VB 809 812 the the DT 813 819 nature nature NN 820 822 of of IN 823 826 the the DT 827 830 A6H A6H NNP 831 834 mAb mab NN 835 845 costimulus costimulus NN 846 848 at at IN 849 852 the the DT 853 868 transcriptional transcriptional JJ 869 874 level level NN 875 877 we we PRP 878 882 have have VBP 883 891 examined examine VBN 892 901 induction induction NN 902 904 of of IN 905 908 the the DT 909 922 transcription transcription NN 923 930 factors factor NNS 931 936 OCT-1 oct-1 NN 936 937 , , , 938 942 AP-1 AP-1 NNP 943 946 and and CC 947 955 NF-kappa NF-kappa NNP 956 957 B B NNP 958 963 which which WDT 964 967 are be VBP 968 973 known know VBN 974 976 to to TO 977 979 be be VB 980 995 transcriptional transcriptional JJ 996 1006 regulators regulator NNS 1007 1009 of of IN 1010 1017 several several JJ 1018 1026 cytokine cytokine NN 1027 1030 and and CC 1031 1039 cytokine cytokine NN 1040 1048 receptor receptor NN 1049 1054 genes gene NNS 1054 1055 , , , 1056 1065 including include VBG 1066 1069 the the DT 1070 1074 IL-2 il-2 NN 1075 1078 and and CC 1079 1084 IL-2R il-2r NN 1085 1090 genes gene NNS 1090 1091 . . . 1092 1103 Co-ligation Co-ligation NNP 1104 1106 of of IN 1107 1110 the the DT 1111 1114 A6H A6H NNP 1115 1122 antigen antigen NN 1123 1126 and and CC 1127 1130 the the DT 1131 1134 CD3 cd3 NN 1135 1142 complex complex NN 1143 1150 induced induce VBD 1151 1161 expression expression NN 1162 1164 of of IN 1165 1168 the the DT 1169 1182 transcription transcription NN 1183 1189 factor factor NN 1190 1194 AP-1 ap-1 NN 1195 1197 in in IN 1198 1202 CD4+ cd4+ JJ 1203 1204 T t NN 1205 1210 cells cell NNS 1210 1211 , , , 1212 1219 whereas whereas IN 1220 1222 no no DT 1223 1231 increase increase NN 1232 1234 in in IN 1235 1243 NF-kappa NF-kappa NNP 1244 1245 B B NNP 1246 1249 and and CC 1250 1265 octamer-binding octamer-binding JJ 1266 1267 ( ( ( 1267 1270 Oct Oct NNP 1270 1271 ) ) ) 1272 1280 proteins protein NNS 1281 1284 was be VBD 1285 1289 seen see VBN 1290 1298 compared compare VBN 1299 1301 to to TO 1302 1303 T t NN 1304 1309 cells cell NNS 1310 1320 stimulated stimulate VBN 1321 1325 with with IN 1326 1334 anti-CD3 anti-cd3 NN 1335 1340 alone alone RB 1340 1341 . . . 1342 1353 Furthermore furthermore RB 1353 1354 , , , 1355 1357 no no DT 1358 1367 induction induction NN 1368 1370 of of IN 1371 1375 AP-1 ap-1 NN 1376 1379 was be VBD 1380 1384 seen see VBN 1385 1387 in in IN 1388 1391 A6H A6H NNP 1392 1404 costimulated costimulate VBD 1405 1409 CD8+ cd8+ JJ 1410 1411 T t NN 1412 1417 cells cell NNS 1417 1418 . . . 1419 1424 These these DT 1425 1432 results result NNS 1433 1441 suggests suggest VBZ 1442 1446 that that IN 1447 1451 both both CC 1452 1460 proximal proximal JJ 1461 1466 steps step NNS 1467 1469 in in IN 1470 1474 CD8+ cd8+ JJ 1475 1481 T-cell t-cell NN 1482 1492 activation activation NN 1493 1495 as as RB 1496 1500 well well RB 1501 1503 as as IN 1504 1507 the the DT 1508 1513 later later JJ 1514 1520 phases phase NNS 1521 1524 are be VBP 1525 1537 unresponsive unresponsive JJ 1538 1540 to to TO 1541 1544 A6H a6h NN 1545 1553 ligation ligation NN 1553 1554 . . . 1555 1564 Molecular molecular JJ 1565 1576 differences difference NNS 1577 1579 of of IN 1580 1583 the the DT 1584 1587 A6H A6H NNP 1588 1596 molecule molecule NN 1597 1599 or or CC 1600 1608 distinct distinct JJ 1609 1619 regulation regulation NN 1620 1622 of of IN 1623 1626 the the DT 1627 1630 A6H A6H NNP 1631 1641 transduced transduce VBN 1642 1646 AP-1 ap-1 NN 1647 1657 activation activation NN 1658 1665 pathway pathway NN 1666 1669 may may MD 1670 1675 exist exist VB 1676 1678 in in IN 1679 1683 CD4+ cd4+ JJ 1684 1687 and and CC 1688 1692 CD8+ cd8+ JJ 1693 1694 T t NN 1695 1699 cell cell NN 1700 1714 subpopulations subpopulation NNS 1714 1715 . . .