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Genetic evidence implicates both autoinflammatory processes and autoimmunity against an HLA<\/jats:styled-content>\u2013B*27<\/jats:italic>\u2013restricted autoantigen in immunopathology. In addition to articular symptoms, up to 70% of AS<\/jats:styled-content> patients present with concurrent bowel inflammation, suggesting that adverse interactions between a genetically primed host immune system and the gut microbiome contribute to the disease. Accordingly, this study aimed to characterize adaptive immune responses to antigenic stimuli in AS<\/jats:styled-content>.<\/jats:p><\/jats:sec>Methods<\/jats:title>The peripheral CD<\/jats:styled-content>4 and CD<\/jats:styled-content>8 T cell receptor (TCR<\/jats:styled-content>) repertoire was profiled in AS<\/jats:styled-content> patients (n = 47) and HLA<\/jats:styled-content>\u2013B*27<\/jats:italic>\u2013matched healthy controls (n = 38). Repertoire diversity was estimated using the Normalized Shannon Diversity Entropy (NSDE<\/jats:styled-content>) index, and univariate and multivariate statistical analyses were performed to characterize AS<\/jats:styled-content>\u2010associated clonal signatures. Furthermore, T cell proliferation and cytokine production in response to immunogenic antigen exposure were investigated in vitro in peripheral blood mononuclear cells from AS<\/jats:styled-content> patients (n = 19) and HLA<\/jats:styled-content>\u2013B*27<\/jats:italic>\u2013matched healthy controls (n = 14).<\/jats:p><\/jats:sec>Results<\/jats:title>Based on the NSDE<\/jats:styled-content> measure of sample diversity across CD<\/jats:styled-content>4 and CD<\/jats:styled-content>8 T cell repertoires, AS<\/jats:styled-content> patients showed increased TCR<\/jats:styled-content> diversity compared to healthy controls (for CD<\/jats:styled-content>4 T cells, P<\/jats:italic> = 7.8 \u00d7 10\u22126<\/jats:sup>; for CD<\/jats:styled-content>8 T cells, P<\/jats:italic> = 9.3 \u00d7 10\u22124<\/jats:sup>), which was attributed to a significant reduction in the magnitude of peripheral T cell expansions globally. Upon in vitro stimulation, fewer T cells from AS<\/jats:styled-content> patients than from healthy controls expressed interferon\u2010\u03b3 (for CD<\/jats:styled-content>8 T cells, P<\/jats:italic> = 0.03) and tumor necrosis factor (for CD<\/jats:styled-content>4 T cells, P<\/jats:italic> = 0.01; for CD<\/jats:styled-content>8 T cells, P<\/jats:italic> = 0.002). In addition, the CD<\/jats:styled-content>8 TCR<\/jats:styled-content> signature was altered in HLA<\/jats:styled-content>\u2013B*27<\/jats:italic>+ AS<\/jats:styled-content> patients compared to healthy controls, with significantly expanded Epstein\u2010Barr virus\u2013specific clonotypes (P<\/jats:italic> = 0.03) and cytomegalovirus\u2010specific clonotypes (P<\/jats:italic> = 0.02). HLA\u2013B*27<\/jats:italic>+ AS patients also showed an increased incidence of \u201cpublic\u201d CD8 TCRs, representing identical clonotypes emerging in response to common antigen encounters, including homologous clonotypes matching those previously isolated from individuals with bacterial\u2010induced reactive arthritis.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>The dynamics of peripheral T cell responses in AS patients are altered, suggesting that differential antigen exposure and disrupted adaptive immunity are underlying features of the disease.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41252","type":"journal-article","created":{"date-parts":[[2020,3,12]],"date-time":"2020-03-12T05:53:34Z","timestamp":1583992414000},"page":"1289-1302","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Altered Repertoire Diversity and Disease\u2010Associated Clonal Expansions Revealed by T Cell Receptor Immunosequencing in Ankylosing Spondylitis Patients"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0231-8771","authenticated-orcid":false,"given":"Aimee L.","family":"Hanson","sequence":"first","affiliation":[{"name":"University of Queensland Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik J.","family":"Nel","sequence":"additional","affiliation":[{"name":"University of Queensland Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Bradbury","sequence":"additional","affiliation":[{"name":"Queensland University of Technology and Translational Research Institute Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Phipps","sequence":"additional","affiliation":[{"name":"Queensland University of Technology and Translational Research Institute Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0518-8386","authenticated-orcid":false,"given":"Ranjeny","family":"Thomas","sequence":"additional","affiliation":[{"name":"University of Queensland Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim\u2010Anh","family":"L\u00ea Cao","sequence":"additional","affiliation":[{"name":"University of Melbourne Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony J.","family":"Kenna","sequence":"additional","affiliation":[{"name":"Queensland University of Technology and Translational Research Institute Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A.","family":"Brown","sequence":"additional","affiliation":[{"name":"Queensland University of Technology and Translational Research Institute, Brisbane, Queensland, Australia, and Guy's and St Thomas' NHS Foundation Trust and King's College London NIHR Biomedical Research Centre, King's College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ket387"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2007.17"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.513"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2667"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3502"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8146"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(73)91360-3"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197304052881403"},{"key":"e_1_2_7_10_1","first-page":"2273","article-title":"The evolution of spondyloarthropathies in relation to gut histology, part II. 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