0 11 Involvement involvement NN 12 14 of of IN 15 18 Rel Rel NNP 18 19 , , , 20 23 Fos Fos NNP 23 24 , , , 25 28 and and CC 29 32 Jun Jun NNP 33 41 proteins protein NNS 42 44 in in IN 45 52 binding binding NN 53 61 activity activity NN 62 64 to to TO 65 68 the the DT 69 73 IL-2 il-2 NN 74 82 promoter promoter NN 83 87 CD28 cd28 NN 88 96 response response NN 97 109 element/AP-1 element/ap-1 NN 110 118 sequence sequence NN 119 121 in in IN 122 127 human human JJ 128 129 T t NN 130 135 cells cell NNS 135 136 . . . 138 142 CD28 cd28 NN 143 145 is be VBZ 146 148 an an DT 149 158 important important JJ 159 172 costimulatory costimulatory JJ 173 181 molecule molecule NN 182 184 in in IN 185 188 the the DT 189 199 activation activation NN 200 202 of of IN 203 208 human human JJ 209 210 T t NN 211 216 cells cell NNS 216 217 . . . 218 231 Costimulation costimulation NN 232 234 of of IN 235 236 T t NN 237 242 cells cell NNS 243 250 through through IN 251 255 both both CC 256 259 the the DT 260 262 Ag ag NN 263 271 receptor receptor NN 272 275 and and CC 276 280 CD28 cd28 NN 281 286 leads lead VBZ 287 289 to to TO 290 294 high high JJ 295 300 level level NN 301 305 IL-2 il-2 NN 306 316 production production NN 316 317 , , , 318 323 which which WDT 324 326 is be VBZ 327 332 vital vital JJ 333 335 to to TO 336 339 the the DT 340 351 development development NN 352 354 of of IN 355 357 an an DT 358 364 immune immune JJ 365 373 response response NN 374 376 in in FW 377 381 vivo vivo FW 381 382 . . . 383 391 Previous previous JJ 392 399 reports report NNS 400 404 have have VBP 405 414 suggested suggest VBN 415 418 the the DT 419 423 CD28 cd28 NN 424 435 stimulation stimulation NN 436 447 contributes contribute VBZ 448 450 to to TO 451 454 the the DT 455 465 activation activation NN 466 468 of of IN 469 472 the the DT 473 477 IL-2 il-2 NN 478 486 promoter promoter NN 487 489 by by IN 490 503 up-regulating up-regulate VBG 504 507 the the DT 508 516 activity activity NN 517 519 of of IN 520 527 several several JJ 528 541 transcription transcription NN 542 549 factors factor NNS 549 550 , , , 551 560 including include VBG 561 565 AP-1 ap-1 NN 566 569 and and CC 570 577 nuclear nuclear JJ 578 591 factor-kappaB factor-kappab NN 592 593 ( ( ( 593 607 NF-kappaB)/Rel NF-kappaB)/Rel NNP 608 614 family family NN 615 622 members member NNS 623 625 as as RB 626 630 well well RB 631 633 as as IN 634 636 an an DT 637 652 uncharacterized uncharacterized JJ 653 666 transcription transcription NN 667 673 factor factor NN 674 680 called call VBN 681 685 CD28 cd28 NN 686 694 response response NN 695 702 complex complex NN 702 703 . . . 704 709 While while IN 710 717 several several JJ 718 723 lines line NNS 724 726 of of IN 727 740 investigation investigation NN 741 745 have have VBP 746 755 suggested suggest VBN 756 760 that that IN 761 774 NF-kappaB/Rel NF-kappaB/Rel NNP 775 781 family family NN 782 789 members member NNS 790 794 make make VBP 795 797 up up RP 798 801 the the DT 802 806 CD28 cd28 NN 807 815 response response NN 816 823 complex complex NN 824 837 transcription transcription NN 838 844 factor factor NN 844 845 , , , 846 851 other other JJ 852 856 work work NN 857 860 has have VBZ 861 864 not not RB 865 874 supported support VBN 875 879 this this DT 880 890 conclusion conclusion NN 890 891 . . . 892 898 Recent recent JJ 899 906 studies study NNS 907 914 suggest suggest VBP 915 919 that that IN 920 923 the the DT 924 928 CD28 cd28 NN 929 937 response response NN 938 945 element element NN 946 947 ( ( ( 947 953 CD28RE CD28RE NNP 953 954 ) ) ) 955 959 does do VBZ 960 963 not not RB 964 972 function function VB 973 986 independently independently RB 987 990 but but CC 991 996 works work VBZ 997 1004 instead instead RB 1005 1007 in in IN 1008 1019 conjunction conjunction NN 1020 1024 with with IN 1025 1028 the the DT 1029 1037 adjacent adjacent JJ 1038 1046 promoter promoter NN 1047 1055 proximal proximal JJ 1056 1068 AP-1-binding ap-1-binding JJ 1069 1073 site site NN 1074 1077 and and CC 1078 1082 this this DT 1083 1093 hypothesis hypothesis NN 1094 1096 is be VBZ 1097 1106 confirmed confirm VBN 1107 1111 here here RB 1111 1112 . . . 1113 1117 Also also RB 1118 1120 in in IN 1121 1124 the the DT 1125 1132 current current JJ 1133 1138 study study NN 1138 1139 , , , 1140 1147 binding binding NN 1148 1156 activity activity NN 1157 1159 to to TO 1160 1163 the the DT 1164 1175 CD28RE/AP-1 cd28re/ap-1 NN 1176 1184 sequence sequence NN 1185 1187 of of IN 1188 1191 the the DT 1192 1196 IL-2 il-2 NN 1197 1205 promoter promoter NN 1206 1208 is be VBZ 1209 1218 evaluated evaluate VBN 1218 1219 . . . 1220 1228 Although although IN 1229 1233 four four CD 1234 1242 specific specific JJ 1243 1252 complexes complex NNS 1253 1256 can can MD 1257 1259 be be VB 1260 1268 detected detect VBN 1269 1276 binding bind VBG 1277 1279 to to TO 1280 1284 this this DT 1285 1293 sequence sequence NN 1293 1294 , , , 1295 1299 only only RB 1300 1303 one one CD 1304 1306 of of IN 1307 1312 these these DT 1313 1322 complexes complex NNS 1323 1325 is be VBZ 1326 1334 specific specific JJ 1335 1338 for for IN 1339 1343 both both CC 1344 1347 the the DT 1348 1354 CD28RE cd28re NN 1355 1358 and and CC 1359 1362 the the DT 1363 1371 adjacent adjacent JJ 1372 1376 AP-1 ap-1 NN 1377 1381 site site NN 1381 1382 . . . 1383 1385 Of of IN 1386 1389 the the DT 1390 1403 NF-kappaB/Rel NF-kappaB/Rel NNP 1404 1410 family family NN 1411 1418 members member NNS 1419 1425 tested test VBN 1425 1426 , , , 1427 1431 this this DT 1432 1452 CD28RE/AP-1-specific cd28re/ap-1-specific JJ 1453 1460 complex complex NN 1461 1469 contains contain VBZ 1470 1483 predominantly predominantly RB 1484 1489 c-Rel c-rel NN 1489 1490 , , , 1491 1498 despite despite IN 1499 1502 the the DT 1503 1507 fact fact NN 1508 1512 that that IN 1513 1517 both both CC 1518 1521 p50 p50 NN 1522 1525 and and CC 1526 1530 RelA RelA NNP 1531 1534 can can MD 1535 1546 efficiently efficiently RB 1547 1551 bind bind VB 1552 1554 to to TO 1555 1558 the the DT 1559 1566 CD28RE. CD28RE. NNP 1567 1572 c-Fos c-fos NN 1573 1576 and and CC 1577 1582 c-Jun c-jun NN 1583 1586 are be VBP 1587 1591 also also RB 1592 1597 found find VBN 1598 1600 in in IN 1601 1605 this this DT 1606 1626 CD28RE/AP-1-specific cd28re/ap-1-specific JJ 1627 1634 complex complex NN 1634 1635 . . . 1636 1641 These these DT 1642 1646 data datum NNS 1647 1655 indicate indicate VBP 1656 1660 that that IN 1661 1671 functional functional JJ 1672 1681 complexes complex NNS 1682 1694 encompassing encompass VBG 1695 1699 both both CC 1700 1703 the the DT 1704 1710 CD28RE cd28re NN 1711 1714 and and CC 1715 1718 the the DT 1719 1731 AP-1-binding ap-1-binding JJ 1732 1737 sites site NNS 1738 1747 influence influence VBP 1748 1752 IL-2 il-2 NN 1753 1761 promoter promoter NN 1762 1770 activity activity NN 1771 1773 in in IN 1774 1791 CD28-costimulated cd28-costimulated JJ 1792 1793 T t NN 1794 1799 cells cell NNS 1799 1800 . . .