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While genetic susceptibility has long pointed toward adaptive immunity, the precise cellular pathways linking MHC class I alleles to axial inflammation have remained an enigma. In this article, we review the fundamental molecular and clinical evidence positioning CD8\u2009 and CD4\u2009 T cells as primary pathogenic drivers of disease in the HLA-B*27\u2009+ \u2009patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Recent findings<\/jats:title>\n                    <jats:p>High-throughput T cell receptor (TCR) sequencing and single-cell RNA sequencing have identified \u201cpublic\u201d TRAV21\/TRBV9 TCRs, that are expanded in the inflamed joints and eyes of patients. These clones initiate disease via molecular mimicry, recognizing both microbial and self-peptides presented by HLA-B*27. The clinical success of seniprutug, a monoclonal antibody selectively targeting TRBV9\u2009+\u2009 T cells, provided the first proof-of-concept that these specific clonotypes drive clinical disease. Furthermore, high-resolution profiling has identified CD4 Th17 cells as the dominant producers of IL-17 within the synovial niche, providing a cellular basis for the efficacy of IL-17A and IL-17F blockade.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Summary<\/jats:title>\n                    <jats:p>AS is a disease characterized by convergent cross-reactive T cell responses. The identification of pathogenic TCR signatures and their candidate cognate antigens has moved diagnostics and management toward precision medicine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11926-026-01213-3","type":"journal-article","created":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T10:16:08Z","timestamp":1772705768000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mechanistic Insights from Human Studies in Axial Spondyloarthritis: A T Cell Story"],"prefix":"10.1007","volume":"28","author":[{"given":"Joy","family":"Um","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Paley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,5]]},"reference":[{"issue":"7855","key":"1213_CR1","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1016\/S0140-6736(74)92431-3","volume":"303","author":"DA Brewerton","year":"1974","unstructured":"Brewerton DA, Caffrey M, Nicholls A, Walters D, James DCO. 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