500:-free heavy chains of HLA-B27 undergo a facile conformational change in which the C-terminal end of domain two, consisting of a long helix, becomes subject to a helix-coil transition involving residues 169–181 of the heavy chain, owing to the conformational freedom newly experienced by domain three of the heavy chain when there is no longer any bound light chain, and owing to the consequent rotation around the backbone dihedral angles of residues 167/168. The proposed conformational transition is thought to allow the newly-generated coiled region (incorporating residues 'RRYLENGKETLQR' which have also been found to be naturally bound to HLA-B27 as a 9-mer peptide) to bind to either the peptide-binding cleft of the same polypeptide chain (in an act of self-display) or to the cleft of another polypeptide chain (in an act of cross-display). Cross-display is proposed to lead to the formation of large, soluble, high molecular weight (HMW), degradation-resistant, long-surviving aggregates of the HLA-B27 heavy chain. Together with any homodimers formed either by cross-display or by a disulfide-linked homodimerization mechanism, it is proposed that such HMW aggregates survive on the cell surface without undergoing rapid degradation, and stimulate an immune response. Three previously noted features of HLA-B27, which distinguish it from other heavy chains, underlie the hypothesis: (1) HLA-B27 has been found to be bound to peptides longer than 9-mers, suggesting that the cleft can accommodate a longer polypeptide chain; (2) HLA-B27 has been found to itself contain a sequence that has also been actually discovered to be bound to HLA-B27, as an independent peptide; and (3) HLA-B27 heavy chains lacking
24:
396:(AS) are HLA-B27 positive, although only a small fraction of people with HLA-B27 will develop AS. People who are HLA-B27 positive are more likely to experience early onset AS than HLA-B27 negative individuals. Research is uncovering other genes that predispose to AS and associated diseases, and there are potential environmental factors that may play a role in susceptible individuals.
492:
suggests that B27 heavy chains tend to dimerise and accumulate in the ER, initiating the UPR. Cell surface B27 heavy chains and dimers can bind to regulatory immune receptors such as members of the killer cell immunoglobulin-like receptor family, promoting the survival and differentiation of
368:), 24% of people are HLA-B27 positive, while 1.8% have associated ankylosing spondylitis, compared to 14-16% of Northern Scandinavians in general. In Finland, an estimated 14% of the population is positive for HLA-B27, while more than 95% of patients with
439:
HLA-B27 is the most researched HLA-B allele due to its high relationship with spondyloarthropathies. Although it is not apparent how HLA-B27 promotes disease, theories exist and can be divided between antigen-dependent and antigen-independent categories.
717:
Feldtkeller, Ernst; Khan, Muhammad; van der Heijde, Désirée; van der Linden, Sjef; Braun, Jürgen (March 2003). "Age at disease onset and diagnosis delay in HLA-B27 negative vs. positive patients with ankylosing spondylitis".
448:
These theories consider a specific combination of antigen peptide sequence and the binding groove (B pocket) of HLA-B27 (which will have different properties from the other HLA-B alleles). The
27:
HLA-B*2705-peptide (chain A shown in green cartoon, chain B shown in yellow cartoon) complexed to a fragment of the influenza nucleoprotein NP383-391 (orange, sticks). PDB ID 2BST
1012:"HLA-B27 lacking associated β2-microglobulin rearranges to auto-display or cross-display residues 169-181: a novel molecular mechanism for spondyloarthropathies"
427:
associated spondyloarthritis. The shared association with HLA-B27 leads to increased clustering of these diseases. HLA antigens have been studied in relation to
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is similar, although it suggests that cross-reactivity between some bacterial antigens and self-peptides can break tolerance and lead to autoimmunity.
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Hacquard-Bouder, Cécile; Ittah, Marc; Breban, Maxime (March 2006). "Animal models of HLA-B27-associated diseases: new outcomes".
817:
563:
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1083:"Human Immunodeficiency Virus Controllers: Mechanisms of Durable Virus Control in the Absence of Antiretroviral Therapy"
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23:
96:
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About 1 in 500 people infected with HIV can remain symptom-free for many years without medication, a group known as
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response that cross-reacts with a HLA-B27/self-peptide pair. HLA-B27 can bind peptides at the cell surface. The
1216:
392:, it does not appear to be the sole mediator in the development of disease. Ninety percent of people with
761:
Thomas, Gethin P.; Brown, Matthew A. (January 2010). "Genetics and genomics of ankylosing spondylitis".
1570:
325:
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697:"Vaasa, laboratorio-ohjekirja Ly-Kudosantigeeni B27 (Vaasa, laboratory manual Ly-Tissue antigen B27)"
477:
1209:
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suggests that HLA-B27 has a unique ability to bind antigens from a microorganism that triggers a
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The prevalence of HLA-B27 varies markedly in the global population. For example, about 8% of
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suggests that slow folding during HLA-B27's tertiary structure folding and association with
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497:
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and in animals, there is little evidence of its occurrence in human spondyloarthritis. The
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has not yet been fully elucidated. Though HLA-B27 is associated with a wide range of
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300:(subtypes B*2701-2759) is a class I surface molecule encoded by the B locus in the
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Antigen-independent theories refer to the biochemical properties of HLA-B27. The
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246:
164:
150:
136:
122:
108:
657:
Bjelle, Anders; Cedergren, Bertil; Rantapää Dahlqvist, Solbritt (January 1982).
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M. A. Khan (2010). "HLA and spondyloarthropathies". In
Narinder K. Mehra (ed.).
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558:. New Delhi, India: Jayppee Brothers Medical Publishers. pp. 259–275.
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361:
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581:"The prevalence of ankylosing spondylitis among Norwegian Samis (Lapps)"
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484:(ER) stress response. Although this mechanism has been demonstrated
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Luthra-Guptasarma, Manni; Singh, Balvinder (24 September 2004).
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descent possess the gene that codes for this antigen. Among the
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313:
579:
Johnsen, K.; Gran, J. T.; Dale, K.; Husby, G. (October 1992).
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Another misfolding theory published in 2004 proposes that
1191:
1140:"HLA B27 in health and disease: a double-edged sword?"
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618:
Gran, J. T.; Mellby, A. S.; Husby, G. (January 1984).
64:
major histocompatibility complex (human), class I, B27
1231:
1081:
Deeks, Steven G.; Walker, Bruce D. (September 2007).
1056:
National
Institute of Allergy and Infectious Diseases
812:. Hagerstwon, MD: Lippincott Williams & Wilkins.
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578:
320:
and other associated inflammatory diseases, such as
476:causes the protein to be misfolded, initiating the
805:
490:HLA-B27 heavy chain homodimer formation hypothesis
1197:National Library of Medicine - Papers on HLA B-27
875:Torres, Anthony; Jonna Westover (February 2012).
1552:
804:Elizabeth D Agabegi; Agabegi, Steven S. (2008).
832:
659:"HLA B 27 in the Population of Northern Sweden"
617:
507:
463:
620:"The Prevalence of HLA-B27 in Northern Norway"
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312:(derived from self and non-self antigens) to
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520:, is significantly common among this group.
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384:The relationship between HLA-B27 and many
372:and approximately 70–80% of patients with
1184:at the U.S. National Library of Medicine
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1027:
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493:pro-inflammatory leukocytes in disease.
399:HLA-B27 is implicated in other types of
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58:
50:
22:
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968:
556:The HLA Complex in Biology and Medicine
542:
379:
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516:. The presence of HLA-B27, as well as
316:. HLA-B27 is strongly associated with
1205:
1074:
1052:"HIV+ Long-Term Non-Progressor Study"
988:10.1146/annurev-immunol-032414-112110
964:
962:
877:"HLA Immune Function Genes in Autism"
808:Step-Up to Medicine (Step-Up Series)
663:Scandinavian Journal of Rheumatology
624:Scandinavian Journal of Rheumatology
1173:Online Mendelian Inheritance in Man
833:Kataria, RK; Brent LH (June 2004).
689:
13:
959:
14:
1582:
1192:BASDAI and Ankylosing Spondylitis
1119:
504:have been seen on cell surfaces.
298:Human leukocyte antigen (HLA) B27
775:10.1111/j.0105-2896.2009.00852.x
450:arthritogenic peptide hypothesis
401:seronegative spondyloarthropathy
302:major histocompatibility complex
1058:. June 23, 2010. Archived from
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969:Bowness, Paul (21 March 2015).
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35:B*2705-β2MG with bound peptide
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1:
1157:10.1093/rheumatology/41.8.857
1138:Bowness, P. (1 August 2002).
1134:by A. Luisa Di Lorenzo, MBBCh
1029:10.1016/j.febslet.2004.08.037
881:Autism Research and Treatment
535:
352:, and 0.1–0.5% of persons of
335:
1100:10.1016/j.immuni.2007.08.010
945:10.1016/j.jbspin.2005.03.016
508:HIV long-term nonprogressors
464:Antigen-independent theories
458:molecular mimicry hypothesis
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20:
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975:Annual Review of Immunology
585:The Journal of Rheumatology
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10:
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720:Rheumatology International
480:(UPR), a pro-inflammatory
444:Antigen-dependent theories
326:inflammatory bowel disease
73:B*2701, 2702, 2703, . . .
1247:
839:American Family Physician
732:10.1007/s00296-002-0237-4
675:10.3109/03009748209098109
636:10.3109/03009748409100382
478:unfolded protein response
376:have the genetic marker.
54:
46:
33:
21:
1186:Medical Subject Headings
699:(in Finnish). 2014-07-21
514:long-term nonprogressors
1561:Immune system disorders
835:"Spondyloarthropathies"
530:Human leukocyte antigen
308:and presents antigenic
435:Pathological mechanism
394:ankylosing spondylitis
370:ankylosing spondylitis
318:ankylosing spondylitis
28:
763:Immunological Reviews
482:endoplasmic reticulum
470:misfolding hypothesis
26:
380:Disease associations
894:10.1155/2012/959073
417:psoriatic arthritis
322:psoriatic arthritis
425:ulcerative colitis
405:reactive arthritis
374:reactive arthritis
330:reactive arthritis
259:2009-02-20 at the
245:2009-02-20 at the
163:2009-02-20 at the
149:2009-02-20 at the
135:2009-02-20 at the
121:2009-02-20 at the
107:2009-02-20 at the
29:
1571:Medical mnemonics
1548:
1547:
1127:HLA-B27 Syndromes
887:(12): 2853–2860.
845:(12): 2853–2860.
819:978-0-7817-7153-5
591:(10): 1591–1594.
565:978-81-8448-870-8
407:, acute anterior
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1062:on July 19, 2011
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933:Joint Bone Spine
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853:. Archived from
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1150:(8): 857–868.
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1120:External links
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1144:Rheumatology
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1064:. Retrieved
1060:the original
1046:
1022:(1–3): 1–8.
1019:
1016:FEBS Letters
1015:
1005:
981:(1): 29–48.
978:
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859:. Retrieved
855:the original
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726:(2): 61–66.
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701:. Retrieved
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360:in Northern
339:
306:chromosome 6
297:
296:
79:
362:Scandinavia
1555:Categories
861:2009-06-29
703:2023-04-13
536:References
454:CD8 T-cell
403:, such as
348:, 2–9% of
342:Caucasians
336:Prevalence
1236:serotypes
1132:eMedicine
971:"HLA-B27"
791:205223192
683:0300-9742
644:0300-9742
597:0315-162X
518:HLA-B5701
390:pathology
304:(MHC) on
284:,
271:,
227:,
214:,
201:,
188:,
175:,
89:Available
80:Structure
1175:(OMIM):
1166:12154202
1109:17892849
1087:Immunity
1038:15388324
997:25861975
953:16377230
913:22928105
851:15222650
783:20192999
740:12634937
524:See also
486:in vitro
386:diseases
354:Japanese
344:, 4% of
310:peptides
277:,
257:Archived
243:Archived
220:,
207:,
194:,
181:,
161:Archived
147:Archived
133:Archived
119:Archived
105:Archived
70:Alleles
1182:HLA-B27
1066:July 5,
904:3420779
748:6020403
605:1464873
421:Crohn's
409:uveitis
350:Chinese
314:T cells
290:
233:
97:EBI-HLA
41:
1242:groups
1240:allele
1188:(MeSH)
1177:142830
1164:
1107:
1036:
995:
951:
911:
901:
849:
816:
789:
781:
746:
738:
681:
642:
603:
595:
562:
429:autism
413:iritis
328:, and
254:B*2709
240:B*2706
158:B*2705
144:B*2704
130:B*2703
116:B*2702
102:B*2701
1252:HLA-B
1233:HLA-B
787:S2CID
744:S2CID
366:Sápmi
84:HLA-B
82:(See
1540:B*83
1535:B*82
1238:and
1162:PMID
1105:PMID
1068:2011
1034:PMID
993:PMID
949:PMID
909:PMID
885:2012
847:PMID
814:ISBN
779:PMID
736:PMID
679:ISSN
640:ISSN
601:PMID
593:ISSN
560:ISBN
423:and
358:Sami
287:1k5n
281:1of2
274:1uxw
268:1w0w
230:1jge
224:1jgd
217:1hsa
211:1ogt
204:1uxs
198:1w0v
191:2a83
185:2bst
178:2bss
172:2bsr
38:2bst
1530:B81
1525:B78
1520:B73
1515:B67
1510:B59
1505:B53
1500:B48
1495:B47
1490:B46
1485:B42
1480:B41
1473:B61
1468:B60
1463:B40
1458:B37
1453:B35
1448:B27
1441:B56
1436:B55
1431:B54
1426:B22
1419:B50
1414:B49
1409:B21
1404:B18
1397:B58
1392:B57
1387:B17
1380:B39
1375:B38
1370:B16
1363:B77
1358:B76
1353:B75
1348:B72
1343:B71
1338:B70
1333:B63
1328:B62
1323:B15
1316:B65
1311:B64
1306:B14
1301:B13
1294:B45
1289:B44
1284:B12
1267:B52
1262:B51
1152:doi
1130:at
1095:doi
1024:doi
1020:575
983:doi
941:doi
899:PMC
889:doi
771:doi
767:233
728:doi
671:doi
632:doi
1557::
1279:B8
1274:B7
1257:B5
1160:.
1148:41
1146:.
1142:.
1103:.
1091:27
1089:.
1085:.
1054:.
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991:.
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