{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T16:46:25Z","timestamp":1784047585741,"version":"3.55.0"},"reference-count":15,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2008,10,30]],"date-time":"2008-10-30T00:00:00Z","timestamp":1225324800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2008,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The class I major histocompatibility complex (MHC) molecule HLA\u2013B27 exhibits a strong association with the autoimmune inflammatory arthritis disorder ankylosing spondylitis (AS) and with other related spondylarthropathies. In the absence of both a defined autoimmune response and a target autoantigen(s), the propensity of HLA\u2013B27 to misfold has been hypothesized to be a major parameter in disease pathogenesis. We undertook this study to test the hypothesis that HLA\u2013B27 misfolding is due to exposure of cysteine residues within the heavy chain to the oxidizing environment of the endoplasmic reticulum.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A rapid acidification and alkylation modification method was used to examine cysteine residue exposure and accessibility within AS\u2010associated and non\u2010AS\u2013associated HLA\u2013B27 subtypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>This novel approach to probing in vivo class I MHC structure revealed that the HLA\u2013B27 heavy chain adopts conformations not previously described. Furthermore, amino acid residues specific to subtypes HLA\u2013B*2706, B*2709, and B*2704 can have an impact on these novel conformations and on cysteine residue exposure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>HLA\u2013B27 can adopt novel conformations, resulting in differential accessibility of cysteine residues, which can explain the propensity to misfold. Cysteine exposure in the HLA\u2013B27 heavy chain is also affected by residues within the 114 and 116 regions, thereby providing a potential biochemical basis for the association of HLA\u2013B27 subtypes with AS.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.23990","type":"journal-article","created":{"date-parts":[[2008,10,30]],"date-time":"2008-10-30T10:59:59Z","timestamp":1225364399000},"page":"3419-3424","source":"Crossref","is-referenced-by-count":25,"title":["Novel detection of in vivo HLA\u2013B27 conformations correlates with ankylosing spondylitis association"],"prefix":"10.1002","volume":"58","author":[{"given":"Helen","family":"Fussell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren","family":"Nesbeth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izabela","family":"Lenart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine C.","family":"Campbell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Lynch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Gould","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon J.","family":"Powis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antony N.","family":"Antoniou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,10,30]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(73)91360-3"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197304052881403"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0039.2002.600301.x"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22821"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22819"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(02)00304-7"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M311757200"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80907-1"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/21.11.2655"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.22.6288"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0198-8859(00)00220-2"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.3.1699"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830231233"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.5.2942"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2004.08.037"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.23990","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.23990","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T16:58:23Z","timestamp":1696957103000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.23990"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,10,30]]},"references-count":15,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2008,11]]}},"alternative-id":["10.1002\/art.23990"],"URL":"https:\/\/doi.org\/10.1002\/art.23990","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,10,30]]}}}