20:
32:
939:
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,
194:
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
211:
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
227:
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
86:
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.
903:
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".
619:
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).
317:
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.
90:
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.
824:
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
155:
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".
992:
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".
1100:
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
586:
62:
of an antibody. These heavy chain types vary between different animals. All heavy chains contain a series of
35:
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
63:
1460:
1214:
868:
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
1237:
1202:
451:
Haas, Ingrid G.; Wabl, Matthias (1983). "Immunoglobulin heavy chain binding protein".
1291:
1242:
1183:
1117:
1082:
1031:
1013:
971:
921:
885:
842:
806:
739:
704:
651:
560:
519:
476:
433:
415:
411:
374:
67:
27:
to two Ig light chains (green). The constant (C) and variable (V) domains are shown.
572:
1396:
1391:
1386:
1381:
1376:
1371:
1281:
1273:
1232:
1222:
1173:
1165:
1105:
1072:
1062:
1021:
1005:
961:
953:
913:
877:
854:
834:
796:
778:
731:
696:
641:
633:
552:
488:
468:
423:
407:
109:
512:
1277:
675:
507:
260:
256:
1152:
Zhang, Tianyi; Tacchi, Luca; Wei, Zhiguo; Zhao, Yaofeng; Salinas, Irene (2014).
171:, but is the same for all immunoglobulins produced by the same B cell or B cell
637:
208:
54:
A typical antibody is composed of two immunoglobulin (Ig) heavy chains and two
24:
1169:
1109:
957:
917:
881:
735:
700:
668:
306:
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).
472:
271:
229:
158:
Heavy chains μ and ε have a constant region composed of four domains.
556:
203:. Thus, where in humans the somatic hypermutation step targets the
1357:
838:
249:
241:
213:
196:
48:
245:
75:
19:
31:
294:, an antibody lacking light chains, and can be used to produce
168:
938:
823:
255:
The heavy chain (δ) for IgD was identified initially from the
1434:
1326:
1201:
Ota, T.; Rast, J. P.; Litman, G. W.; Amemiya, C. T. (2003).
1453:
1448:
1422:
1417:
902:
207:
process, the target in cows is on the creation of diverse
125:
121:
117:
113:
278:(IgT or IgZ) that may precede IgM in evolutionary terms.
135:
Heavy chains μ and ε have approximately 550 amino acids.
132:
Heavy chains α and γ have approximately 450 amino acids.
757:
Hansen, J. D.; Landis, E. D.; Phillips, R. B. (2005).
1259:
1049:
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:. Retrieved
590:
581:
551:(2): 89–99.
548:
544:
538:
513:
456:
452:
446:
403:
399:
389:
363:. 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:(
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.