{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T06:20:36Z","timestamp":1791181236103,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2010,6,7]],"date-time":"2010-06-07T00:00:00Z","timestamp":1275868800000},"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":[[2010,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>HLA\u2013DRB1*1001 (DR1001) is a shared epitope allele associated with rheumatoid arthritis (RA). The present study was undertaken to assess the capacity of DR1001 to accommodate citrulline in its binding pockets and to identify citrullinated T cell epitopes derived from joint\u2010associated proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The binding of peptide derivatives containing citrulline, arginine, and other amino acid substitutions was measured. A prediction algorithm was developed to identify arginine\u2010containing sequences from joint\u2010associated proteins that preferentially bind to DR1001 upon citrullination. Unmodified and citrullinated versions of these sequences were synthesized and were utilized to stimulate CD4+ T cells from healthy subjects and RA patients. Responses were measured by class II major histocompatibility complex tetramer staining and confirmed by isolating CD4+ T cell clones.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>DR1001 accepted citrulline, but not arginine, in 3 of its anchoring pockets. The prediction algorithm identified sequences that preferentially bound to DR1001 with arginine replaced by citrulline. Three of these sequences elicited CD4+ T cell responses. T cell clones specific for these sequences proliferated only in response to citrullinated peptides.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Conversion of arginine to citrulline generates \u201caltered\u2010self\u201d peptides that can be bound and presented by DR1001. Responses to these peptides implicate the corresponding proteins (fibrinogen \u03b1, fibrinogen \u03b2, and cartilage intermediate\u2010layer protein) as relevant antigens. The finding of preferential responses to citrullinated sequences suggests that altered peptide binding affinity due to this posttranslational modification may be an important factor in the initiation or progression of RA. As such, measuring responsiveness to these peptides may be useful for immunologic monitoring.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.27594","type":"journal-article","created":{"date-parts":[[2010,6,7]],"date-time":"2010-06-07T15:48:10Z","timestamp":1275925690000},"page":"2909-2918","source":"Crossref","is-referenced-by-count":95,"title":["HLA\u2013DR1001 presents \u201caltered\u2010self\u201d peptides derived from joint\u2010associated proteins by accepting citrulline in three of its binding pockets"],"prefix":"10.1002","volume":"62","author":[{"given":"Eddie A.","family":"James","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonis K.","family":"Moustakas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Bui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George 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