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Immunoglobulin heavy chain

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Wesolowski, Janusz; Alzogaray, Vanina; Reyelt, Jan; Unger, Mandy; Juarez, Karla; Urrutia, Mariela; Cauerhff, Ana; Danquah, Welbeck; Rissiek, Björn; Scheuplein, Felix; Schwarz, Nicole; Adriouch, Sahil; Boyer, Olivier; Seman, Michel; Licea, Alexei; Serreze, David V.; Goldbaum, Fernando A.; Haag,
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has adapted to produce a divergent repertoire of antibodies which present a "stalk and knob" antigen interaction surface instead of the more familiar bivalent tip surface. The bovine CDR is unusually long and contains unique sequence attributes which support the production of paired
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and the generation of unique sets of loops which interact with antigen. A speculated evolutionary driver for this variation is the presence of a vastly more diverse microbial environment in the digestive system of the cow as a consequence of their being
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appear to be the most primitive animals that are able to make antibodies like those described for mammals. However, fish do not have the same repertoire of antibodies that mammals possess. Three distinct Ig heavy chains have so far been identified in
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2, etc.). Production of a viable heavy chain is a key step in B cell maturation. If the heavy chain is able to bind to a surrogate light chain and move to the plasma membrane, then the developing B cell can begin producing its light chain.
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Simmons, David P.; Abregu, Fiona A.; Krishnan, Usha V.; Proll, David F.; Streltsov, Victor A.; Doughty, Larissa; Hattarki, Meghan K.; Nuttall, Stewart D. (2006). "Dimerisation strategies for shark IgNAR single domain antibody fragments".
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Wang, Feng; Ekiert, Damian C.; Ahmad, Insha; Yu, Wenli; Zhang, Yong; Bazirgan, Omar; Torkamani, Ali; Raudsepp, Terje; Mwangi, Waithaka; Criscitiello, Michael F.; Wilson, Ian A.; Schultz, Peter G.; Smider, Vaughn V. (2013).
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IgW has now also been found in the group of lobe finned fishes including the coelacanth and lungfish. The IgW1 and IgW2 in coelacanth has a usual (VD)n-Jn-C structure as well as having a large number of constant domains.
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The heavy chain does not always have to bind to a light chain. Pre-B lymphocytes can synthesize heavy chain in the absence of light chain, which then can allow the heavy chain to bind to a heavy-chain binding protein.
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Danilova, Nadia; Bussmann, Jeroen; Jekosch, Kerstin; Steiner, Lisa A (2005). "The immunoglobulin heavy-chain locus in zebrafish: Identification and expression of a previously unknown isotype, immunoglobulin Z".
286:. With the exception of μ, these Ig heavy chain isotypes appear to be unique to cartilaginous fish. The resulting antibodies are designated IgW (also called IgX or IgNARC) and IgNAR ( 266:
The third teleost Ig heavy chain gene was identified very recently and does not resemble any of the heavy chains so far described for mammals. This heavy chain, identified in both
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Heavy chains γ, α and δ have a constant region composed of three tandem (in a line next to each other) immunoglobulin domains but also have a hinge region for added flexibility.
240:) heavy chain that is present in all jawed fish and is the heavy chain for what is thought to be the primordial immunoglobulin. The resulting antibody, IgM, is secreted as a 1051:"Ancient species offers contemporary therapeutics: an update on shark VNAR single domain antibody sequences, phage libraries and potential clinical applications" 687:
Bengtén, Eva; Clem, L. William; Miller, Norman W.; Warr, Gregory W.; Wilson, Melanie (2006). "Channel catfish immunoglobulins: Repertoire and expression".
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Feng, Mingqian; Bian, Hejiao; Wu, Xiaolin; Fu, Tianyun; Fu, Ying; Hong, Jessica; Fleming, Bryan D.; Flajnik, Martin F.; Ho, Mitchell (January 2019).
759:"Discovery of a unique Ig heavy-chain isotype (IgT) in rainbow trout: Implications for a distinctive B cell developmental pathway in teleost fish" 994:"Construction and next-generation sequencing analysis of a large phage-displayed VNAR single-domain antibody library from six naïve nurse sharks" 722:
Solem, Stein Tore; Stenvik, Jørgen (2006). "Antibody repertoire development in teleosts—a review with emphasis on salmonids and Gadus morhua L".
354: 380: 175:. The variable domain of any heavy chain is composed of a single immunoglobulin domain. These domains are about 110 amino acids long. 1203:"Lineage-restricted retention of a primitive immunoglobulin heavy chain isotype within the Dipnoi reveals an evolutionary paradox" 529: 1348: 671: 543:
Woof, Jenny M.; Burton, Dennis R. (2004). "Human antibody–Fc receptor interactions illuminated by crystal structures".
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Li, Dan; English, Hejiao; Hong, Jessica; Liang, Tianyuzhou; Merlino, Glenn; Day, Chi-Ping; Ho, Mitchell (2021-07-21).
523: 1102:"A novel PD-L1-targeted shark VNAR single domain-based CAR-T strategy for treating breast cancer and liver cancer" 282:
Similar to the situation observed for bony fish, three distinct Ig heavy chain isotypes have been identified in
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of an antibody. These heavy chain types vary between different animals. All heavy chains contain a series of
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An antibody molecule. The two heavy chains are colored red and blue and the two light chains green and yellow.
1321: 1262:"Oral immunization of the African clawed frog (Xenopus laevis) upregulates the mucosal immunoglobulin IgX" 1412: 1311: 55: 1138: 1341: 1315: 295: 942:"Single domain antibodies: Promising experimental and therapeutic tools in infection and immunity" 358: 1482: 172: 1101: 1125: 200: 104:
There are five types of mammalian immunoglobulin heavy chain: γ, δ, α, μ and ε. They define
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Dooley, H.; Flajnik, M.F. (2006). "Antibody repertoire development in cartilaginous fish".
770: 460: 396:"Role of the surrogate light chain and the pre-B-cell receptor in mouse B-cell development" 335: 291: 275: 152:(which is the same for all immunoglobulins of the same class but differs between classes). 59: 8: 1334: 204: 1218: 1154:"Intraclass diversification of immunoglobulin heavy chain genes in the African lungfish" 774: 464: 1286: 1261: 1178: 1153: 1113: 1077: 1050: 1026: 993: 966: 941: 850: 801: 788: 758: 646: 621: 568: 484: 428: 395: 283: 23:
Schematic diagram of a typical antibody showing two Ig heavy chains (purple) joined by
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Haas, Ingrid G.; Wabl, Matthias (1983). "Immunoglobulin heavy chain binding protein".
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to two Ig light chains (green). The constant (C) and variable (V) domains are shown.
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Zhang, Tianyi; Tacchi, Luca; Wei, Zhiguo; Zhao, Yaofeng; Salinas, Irene (2014).
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A typical antibody is composed of two immunoglobulin (Ig) heavy chains and two
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s) to tumor or viral antigens can be isolated from a large naïve nurse shark V
1476: 1017: 419: 311: 267: 191: 1227: 783: 1295: 1246: 1187: 1086: 1035: 975: 925: 889: 846: 810: 743: 708: 655: 564: 437: 190:, show a variation on the general mammalian theme in which the heavy chain 51:(immunoglobulin). In human genome, the IgH gene loci are on chromosome 14. 1067: 480: 1009: 58:. Several different types of heavy chain exist that define the class or 792: 224: 186: 1260:
Du, Christina C.; Mashoof, Sara M.; Criscitiello, Michael F. (2012).
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Heavy chains μ and ε have a constant region composed of four domains.
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The heavy chain (δ) for IgD was identified initially from the
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Ota, T.; Rast, J. P.; Litman, G. W.; Amemiya, C. T. (2003).
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process, the target in cows is on the creation of diverse
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Heavy chains μ and ε have approximately 550 amino acids.
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Heavy chains α and γ have approximately 450 amino acids.
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Hansen, J. D.; Landis, E. D.; Phillips, R. B. (2005).
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English, Hejiao; Hong, Jessica; Ho, Mitchell (2020).
686: 1200: 756: 1151: 1099: 511: 618: 393: 263:and is now well documented for many teleost fish. 1474: 302:) of an IgNAR. Shark single domain antibodies (V 274:(ζ), could potentially form a distinct antibody 1207:Proceedings of the National Academy of Sciences 763:Proceedings of the National Academy of Sciences 506: 298:, which are essentially the variable domain (V 1342: 1322:Educational Resource for Heavy Chain Analysis 1048: 867: 991: 721: 1349: 1335: 870:Developmental & Comparative Immunology 724:Developmental & Comparative Immunology 689:Developmental & Comparative Immunology 614: 612: 610: 608: 542: 502: 500: 498: 394:Mårtensson, I-L; Ceredig, R (2017-01-23). 1314:at the U.S. National Library of Medicine 1285: 1266:Veterinary Immunology and Immunopathology 1236: 1226: 1177: 1076: 1066: 1025: 965: 940:Friedrich; Koch-Nolte, Friedrich (2009). 800: 782: 645: 530:(electronic full text via NCBI Bookshelf) 427: 47:) is the large polypeptide subunit of an 450: 30: 18: 16:Large polypeptide subunit of an antibody 605: 495: 1475: 669:Fish heavy chain and light chain genes 379:: CS1 maint: archived copy as title ( 1330: 987: 985: 518:(5th ed.). Garland Publishing. 326:Frogs can synthesize IgX and IgY. 946:Medical Microbiology and Immunology 536: 444: 288:immunoglobulin new antigen receptor 236:The first identified was the μ (or 13: 982: 144:Each heavy chain has two regions: 14: 1494: 1305: 906:Journal of Immunological Methods 412:10.1046/j.1365-2567.2000.00151.x 321: 74:) that is important for binding 1253: 1194: 1145: 1093: 1042: 932: 896: 861: 817: 750: 715: 167:that differs between different 78:and several constant domains (C 1356: 680: 662: 622:"Reshaping Antibody Diversity" 579: 387: 347: 1: 341: 94: 1278:10.1016/j.vetimm.2011.10.019 252:found in mammals and sharks. 248:fish instead of the typical 66:, usually with one variable 7: 1312:Immunoglobulin+Heavy+Chains 593:. The University of Arizona 329: 10: 1499: 638:10.1016/j.cell.2013.04.049 219: 139: 99: 41:immunoglobulin heavy chain 1405: 1364: 1170:10.1007/s00251-014-0769-2 1110:10.1101/2021.07.20.453144 958:10.1007/s00430-009-0116-7 918:10.1016/j.jim.2006.07.019 882:10.1016/j.dci.2005.06.022 736:10.1016/j.dci.2005.06.007 701:10.1016/j.dci.2005.06.016 545:Nature Reviews Immunology 1316:Medical Subject Headings 312:phage display technology 296:single-domain antibodies 290:). The latter type is a 1228:10.1073/pnas.0538029100 784:10.1073/pnas.0500027102 674:March 23, 2007, at the 179: 1133:Cite journal requires 510:; et al. (2001). 64:immunoglobulin domains 36: 28: 1104:: 2021.07.20.453144. 1055:Antibody Therapeutics 998:Antibody Therapeutics 587:"The Biology Project" 201:somatic hypermutation 34: 22: 1461:Heavy-chain antibody 336:Heavy-chain antibody 292:heavy-chain antibody 108:of immunoglobulins: 1219:2003PNAS..100.2501O 1068:10.1093/abt/tbaa001 775:2005PNAS..102.6919H 465:1983Natur.306..387H 205:V(D)J recombination 184:Cows, specifically 1010:10.1093/abt/tby011 591:Antibody Structure 284:cartilaginous fish 37: 29: 1470: 1469: 827:Nature Immunology 769:(19): 6919–6924. 361:on April 19, 2007 128:, respectively. 1490: 1351: 1344: 1337: 1328: 1327: 1300: 1299: 1289: 1257: 1251: 1250: 1240: 1230: 1198: 1192: 1191: 1181: 1149: 1143: 1142: 1136: 1131: 1129: 1121: 1097: 1091: 1090: 1080: 1070: 1046: 1040: 1039: 1029: 989: 980: 979: 969: 936: 930: 929: 900: 894: 893: 865: 859: 858: 821: 815: 814: 804: 786: 754: 748: 747: 719: 713: 712: 684: 678: 666: 660: 659: 649: 616: 603: 602: 600: 598: 583: 577: 576: 540: 534: 533: 517: 504: 493: 492: 473:10.1038/306387a0 448: 442: 441: 431: 391: 385: 384: 378: 370: 368: 366: 357:. Archived from 351: 199:residues during 1498: 1497: 1493: 1492: 1491: 1489: 1488: 1487: 1473: 1472: 1471: 1466: 1401: 1360: 1355: 1308: 1303: 1258: 1254: 1199: 1195: 1150: 1146: 1134: 1132: 1123: 1122: 1098: 1094: 1047: 1043: 990: 983: 937: 933: 912:(1–2): 171–84. 901: 897: 866: 862: 822: 818: 755: 751: 720: 716: 685: 681: 676:Wayback Machine 667: 663: 617: 606: 596: 594: 585: 584: 580: 557:10.1038/nri1266 541: 537: 526: 508:Janeway CA, Jr. 505: 496: 459:(5941): 387–9. 449: 445: 392: 388: 372: 371: 364: 362: 355:"Archived copy" 353: 352: 348: 344: 332: 324: 309: 305: 301: 261:Atlantic salmon 257:channel catfish 222: 209:disulfide bonds 182: 165:variable region 150:constant region 142: 102: 97: 85: 81: 73: 56:Ig light chains 25:disulfide bonds 17: 12: 11: 5: 1496: 1486: 1485: 1468: 1467: 1465: 1464: 1458: 1457: 1456: 1451: 1440: 1439: 1438: 1437: 1427: 1426: 1425: 1420: 1409: 1407: 1403: 1402: 1400: 1399: 1394: 1389: 1384: 1379: 1374: 1368: 1366: 1362: 1361: 1354: 1353: 1346: 1339: 1331: 1325: 1324: 1319: 1307: 1306:External links 1304: 1302: 1301: 1272:(1–2): 493–8. 1252: 1193: 1158:Immunogenetics 1144: 1135:|journal= 1092: 1041: 981: 931: 895: 876:(1–2): 43–56. 860: 839:10.1038/ni1166 833:(3): 295–302. 816: 749: 730:(1–2): 57–76. 714: 695:(1–2): 77–92. 679: 661: 632:(6): 1379–93. 604: 578: 535: 524: 494: 443: 406:(4): 435–441. 386: 345: 343: 340: 339: 338: 331: 328: 323: 320: 310:library using 307: 303: 299: 280: 279: 264: 253: 221: 218: 181: 178: 177: 176: 161: 160: 159: 156: 141: 138: 137: 136: 133: 101: 98: 96: 93: 83: 79: 71: 15: 9: 6: 4: 3: 2: 1495: 1484: 1483:Immune system 1481: 1480: 1478: 1462: 1459: 1455: 1452: 1450: 1447: 1446: 1445: 1442: 1441: 1436: 1433: 1432: 1431: 1428: 1424: 1421: 1419: 1416: 1415: 1414: 1411: 1410: 1408: 1404: 1398: 1395: 1393: 1390: 1388: 1385: 1383: 1380: 1378: 1375: 1373: 1370: 1369: 1367: 1363: 1359: 1352: 1347: 1345: 1340: 1338: 1333: 1332: 1329: 1323: 1320: 1317: 1313: 1310: 1309: 1297: 1293: 1288: 1283: 1279: 1275: 1271: 1267: 1263: 1256: 1248: 1244: 1239: 1234: 1229: 1224: 1220: 1216: 1213:(5): 2501–6. 1212: 1208: 1204: 1197: 1189: 1185: 1180: 1175: 1171: 1167: 1164:(5): 335–51. 1163: 1159: 1155: 1148: 1140: 1127: 1119: 1115: 1111: 1107: 1103: 1096: 1088: 1084: 1079: 1074: 1069: 1064: 1060: 1056: 1052: 1045: 1037: 1033: 1028: 1023: 1019: 1015: 1011: 1007: 1003: 999: 995: 988: 986: 977: 973: 968: 963: 959: 955: 952:(3): 157–74. 951: 947: 943: 935: 927: 923: 919: 915: 911: 907: 899: 891: 887: 883: 879: 875: 871: 864: 856: 852: 848: 844: 840: 836: 832: 828: 820: 812: 808: 803: 798: 794: 790: 785: 780: 776: 772: 768: 764: 760: 753: 745: 741: 737: 733: 729: 725: 718: 710: 706: 702: 698: 694: 690: 683: 677: 673: 670: 665: 657: 653: 648: 643: 639: 635: 631: 627: 623: 615: 613: 611: 609: 592: 588: 582: 574: 570: 566: 562: 558: 554: 550: 546: 539: 531: 527: 525:0-8153-3642-X 521: 516: 515: 514:Immunobiology 509: 503: 501: 499: 490: 486: 482: 478: 474: 470: 466: 462: 458: 454: 447: 439: 435: 430: 425: 421: 417: 413: 409: 405: 401: 397: 390: 382: 376: 360: 356: 350: 346: 337: 334: 333: 327: 322:In amphibians 319: 315: 313: 297: 293: 289: 285: 277: 273: 269: 268:rainbow trout 265: 262: 258: 254: 251: 247: 243: 239: 235: 234: 233: 231: 226: 217: 215: 210: 206: 202: 198: 193: 192:CDR H3 region 189: 188: 174: 170: 166: 162: 157: 154: 153: 151: 147: 146: 145: 134: 131: 130: 129: 127: 123: 119: 115: 111: 107: 92: 88: 77: 69: 65: 61: 57: 52: 50: 46: 42: 33: 26: 21: 1443: 1429: 1269: 1265: 1255: 1210: 1206: 1196: 1161: 1157: 1147: 1126:cite journal 1095: 1058: 1054: 1044: 1001: 997: 949: 945: 934: 909: 905: 898: 873: 869: 863: 830: 826: 819: 766: 762: 752: 727: 723: 717: 692: 688: 682: 664: 629: 625: 595:. 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Retrieved 359:the original 349: 325: 316: 287: 281: 237: 223: 185: 183: 164: 149: 143: 105: 103: 89: 53: 44: 40: 38: 1444:Heavy chain 1413:Light chain 1004:(1): 1–11. 1365:Main types 1358:Antibodies 1061:(1): 1–9. 400:Immunology 342:References 225:Jawed fish 187:Bos taurus 95:In mammals 1430:surrogate 1118:236203365 1018:2516-4236 420:0019-2805 365:April 20, 272:zebrafish 230:bony fish 214:ruminants 1477:Category 1296:22100190 1247:12606718 1188:24676685 1087:32118195 1036:30627698 976:19529959 926:16962608 890:16146649 847:15685175 811:15863615 744:16084588 709:16153707 672:Archived 656:23746848 573:30584218 565:15040582 438:11122446 375:cite web 330:See also 270:(τ) and 250:pentamer 242:tetramer 197:cysteine 49:antibody 1287:3273591 1215:Bibcode 1179:4348116 1078:7034638 1027:6312525 967:2714450 855:5543330 802:1100771 793:3375456 771:Bibcode 647:4007204 597:May 27, 489:4247626 481:6417546 461:Bibcode 429:2327112 276:isotype 246:teleost 220:In fish 169:B cells 140:Regions 106:classes 100:Classes 76:antigen 60:isotype 1463:/IgNAR 1406:Chains 1318:(MeSH) 1294:  1284:  1245:  1238:151370 1235:  1186:  1176:  1116:  1085:  1075:  1034:  1024:  1016:  974:  964:  924:  888:  853:  845:  809:  799:  791:  742:  707:  654:  644:  571:  563:  522:  487:  479:  453:Nature 436:  426:  418:  68:domain 1435:IGLL1 1114:S2CID 851:S2CID 789:JSTOR 569:S2CID 485:S2CID 173:clone 1454:IGHM 1449:IGH@ 1423:IGL@ 1418:IGK@ 1292:PMID 1243:PMID 1184:PMID 1139:help 1083:PMID 1032:PMID 1014:ISSN 972:PMID 922:PMID 886:PMID 843:PMID 807:PMID 740:PMID 705:PMID 652:PMID 626:Cell 599:2020 561:PMID 520:ISBN 477:PMID 434:PMID 416:ISSN 381:link 367:2007 259:and 180:Cows 124:and 82:1, C 39:The 1397:IgY 1392:IgM 1387:IgG 1382:IgE 1377:IgD 1372:IgA 1282:PMC 1274:doi 1270:145 1233:PMC 1223:doi 1211:100 1174:PMC 1166:doi 1106:doi 1073:PMC 1063:doi 1022:PMC 1006:doi 962:PMC 954:doi 950:198 914:doi 910:315 878:doi 835:doi 797:PMC 779:doi 767:102 732:doi 697:doi 642:PMC 634:doi 630:153 553:doi 469:doi 457:306 424:PMC 408:doi 404:101 308:NAR 304:NAR 300:NAR 244:in 126:IgE 122:IgM 118:IgA 114:IgD 110:IgG 45:IgH 1479:: 1290:. 1280:. 1268:. 1264:. 1241:. 1231:. 1221:. 1209:. 1205:. 1182:. 1172:. 1162:66 1160:. 1156:. 1130:: 1128:}} 1124:{{ 1112:. 1081:. 1071:. 1057:. 1053:. 1030:. 1020:. 1012:. 1000:. 996:. 984:^ 970:. 960:. 948:. 944:. 920:. 908:. 884:. 874:30 872:. 849:. 841:. 829:. 805:. 795:. 787:. 777:. 765:. 761:. 738:. 728:30 726:. 703:. 693:30 691:. 650:. 640:. 628:. 624:. 607:^ 589:. 567:. 559:. 547:. 528:. 497:^ 483:. 475:. 467:. 455:. 432:. 422:. 414:. 402:. 398:. 377:}} 373:{{ 314:. 238:mu 232:. 216:. 163:a 148:a 120:, 116:, 112:, 70:(V 1350:e 1343:t 1336:v 1298:. 1276:: 1249:. 1225:: 1217:: 1190:. 1168:: 1141:) 1137:( 1120:. 1108:: 1089:. 1065:: 1059:3 1038:. 1008:: 1002:2 978:. 956:: 928:. 916:: 892:. 880:: 857:. 837:: 831:6 813:. 781:: 773:: 746:. 734:: 711:. 699:: 658:. 636:: 601:. 575:. 555:: 549:4 532:. 491:. 471:: 463:: 440:. 410:: 383:) 369:. 84:H 80:H 72:H 43:(

Index


disulfide bonds

antibody
Ig light chains
isotype
immunoglobulin domains
domain
antigen
IgG
IgD
IgA
IgM
IgE
B cells
clone
Bos taurus
CDR H3 region
cysteine
somatic hypermutation
V(D)J recombination
disulfide bonds
ruminants
Jawed fish
bony fish
tetramer
teleost
pentamer
channel catfish
Atlantic salmon

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