{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:20:05Z","timestamp":1792790405070,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,24]]},"group-title":"Immunology","reference-count":58,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["F30AI200188"],"award-info":[{"award-number":["F30AI200188"]}]},{"name":"National Institutes of Health","award":["T32HG000045"],"award-info":[{"award-number":["T32HG000045"]}]},{"name":"National Institutes of Health","award":["R01CA301054"],"award-info":[{"award-number":["R01CA301054"]}]},{"name":"National Institutes of Health","award":["K08AR079593"],"award-info":[{"award-number":["K08AR079593"]}]},{"name":"National Institutes of Health","award":["P30AR073752"],"award-info":[{"award-number":["P30AR073752"]}]},{"name":"National Institutes of Health","award":["P30DK052574"],"award-info":[{"award-number":["P30DK052574"]}]},{"name":"United States Department of Defense","award":["AT240082"],"award-info":[{"award-number":["AT240082"]}],"id":[{"id":"https:\/\/ror.org\/0447fe631","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Spondylitis Association of America","id":[{"id":"https:\/\/ror.org\/01yxtb033","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Rheumatology Research Foundation","id":[{"id":"https:\/\/ror.org\/03sdr0263","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Edward Mallinckrodt, Jr. Foundation","id":[{"id":"https:\/\/ror.org\/035yf7a66","id-type":"ROR","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/03abbex33","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Doris Duke Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Human leukocyte antigen B*27 (HLA-B*27) is a major risk factor for autoimmune diseases such as axial spondyloarthritis (axSpA), acute anterior uveitis (AAU), and psoriatic arthritis (PsA). HLA-B*27 presents bacterial and self-antigens to disease-associated CD8+ T cells, however, how this leads to a pathogenic IL-17-mediated disease remains unclear. We performed mutational experiments in an established disease-associated TCR and demonstrated that the pathogenic motif encompasses a wider range of TCR sequences than previously appreciated. We next leveraged computational pairing of alpha\/beta TCR sequencing (TCR-seq) to demonstrate that the broadened pathogenic motif distinguishes axSpA and AAU patients from healthy controls. Paired single-cell RNA sequencing and single-cell TCR sequencing datasets demonstrated that the pathogenic cells have a distinct transcriptional signature. We find a coupling of pathogenic TCRs to this transcriptional signature in public datasets from axSpA and PsA joint fluid and AAU ocular fluid. Finally, we detect the pathogenic CD8+ T cells in the gut and demonstrate that they express a Type 17 program. Our findings suggest that HLA-B*27+ axSpA, AAU, and PsA are initiated by HLA-B*27-restricted pathogenic CD8+ T cells that undergo Type 17 differentiation in response to intestinal antigens.<\/jats:p>\n                <jats:sec>\n                  <jats:title>One Sentence Summary<\/jats:title>\n                  <jats:p>Multiple HLA-B*27-associated autoimmune diseases share the same pathogenic CD8+ T cells with Type 17 gene expression and cytokine production.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.18.752092","type":"posted-content","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T23:55:15Z","timestamp":1790294115000},"source":"Crossref","is-referenced-by-count":0,"title":["Refinement of the Pathogenic T Cell Receptor Motif Suggests Type 17 CD8+ T Cells Initiate HLA-B*27-associated Autoimmunity"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3356-0349","authenticated-orcid":false,"given":"Isabel","family":"Risch","sequence":"first","affiliation":[{"name":"Department of Genetics, Washington University School of Medicine; 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