{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T13:41:45Z","timestamp":1787578905909,"version":"build-2736575974"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,1,12]],"date-time":"2020-01-12T00:00:00Z","timestamp":1578787200000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003921","name":"Department of Health, Australian Government","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003921","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["510448"],"award-info":[{"award-number":["510448"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1085875"],"award-info":[{"award-number":["1085875"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001773","name":"University of New South Wales","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001773","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin &amp;amp; Trans Imm"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Understanding the T cell receptor (TCR) repertoire of regulatory CD4<jats:sup>+<\/jats:sup> T\u2010cell (Treg) populations is important for strategies aiming to re\u2010establish tolerance in autoimmune diseases. We studied circulating deamidated gluten\u2010epitope\u2010specific CD39<jats:sup>+<\/jats:sup> Tregs in patients with coeliac disease following an oral gluten challenge, and we used cytomegalovirus (CMV)\u2010specific CD39<jats:sup>+<\/jats:sup> Tregs from healthy controls as a comparator population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used the OX40 assay to isolate antigen\u2010specific Tregs by induced surface co\u2010expression of CD25, OX40 and CD39. RACE PCR amplification and Sanger sequencing of the TCR \u03b2 chain were used to analyse repertoire diversity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that, following oral gluten challenge, circulating gluten\u2010specific CD39<jats:sup>+<\/jats:sup> Tregs had an oligoclonal TCR repertoire that contained public clonotypes. Conversely, the TCR repertoire of CMV\u2010epitope\u2010specific CD39<jats:sup>+<\/jats:sup> Tregs from healthy controls was polyclonal.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These data indicate that a biased TCR repertoire is not inherent to CD39<jats:sup>+<\/jats:sup> Tregs, and, in this case, is apparently driven by the HLA\u2010DQ2.5\u2010restricted deamidated gluten peptide in coeliac disease patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This is the first assessment of the TCR repertoire within circulating human Tregs specific for foreign antigen. These data enhance our understanding of antigen\u2010specific CD4<jats:sup>+<\/jats:sup> responses in the settings of chronic inflammation and infection and may help guide immunomonitoring strategies for CD4<jats:sup>+<\/jats:sup> T cell\u2010based therapies, particularly for coeliac disease.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cti2.1096","type":"journal-article","created":{"date-parts":[[2020,1,13]],"date-time":"2020-01-13T02:49:40Z","timestamp":1578883780000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Circulating gluten\u2010specific, but not CMV\u2010specific, CD39<sup>+<\/sup> regulatory T cells have an oligoclonal TCR repertoire"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3153-2045","authenticated-orcid":false,"given":"Laura","family":"Cook","sequence":"first","affiliation":[{"name":"Immunovirology and Pathogenesis Program The Kirby Institute UNSW Australia Sydney NSW Australia"},{"name":"St Vincent's Centre for Applied Medical Research St Vincent's Hospital Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6419-142X","authenticated-orcid":false,"given":"C Mee Ling","family":"Munier","sequence":"additional","affiliation":[{"name":"Immunovirology and Pathogenesis Program The Kirby Institute UNSW Australia Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0379-8527","authenticated-orcid":false,"given":"Nabila","family":"Seddiki","sequence":"additional","affiliation":[{"name":"Immunovirology and Pathogenesis Program The Kirby Institute UNSW Australia Sydney NSW Australia"},{"name":"St Vincent's Centre for Applied Medical Research St Vincent's Hospital Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4923-0678","authenticated-orcid":false,"given":"Melinda Y","family":"Hardy","sequence":"additional","affiliation":[{"name":"Immunology Division Walter and Eliza Hall Institute Parkville VIC Australia"},{"name":"Department of Medical Biology The University of Melbourne Parkville VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0764-7267","authenticated-orcid":false,"given":"Robert P","family":"Anderson","sequence":"additional","affiliation":[{"name":"Immunology Division Walter and Eliza Hall Institute Parkville VIC Australia"},{"name":"Department of Medical Biology The University of Melbourne Parkville VIC Australia"},{"name":"ImmusanT, Inc. Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Zaunders","sequence":"additional","affiliation":[{"name":"Immunovirology and Pathogenesis Program The Kirby Institute UNSW Australia Sydney NSW Australia"},{"name":"St Vincent's Centre for Applied Medical Research St Vincent's Hospital Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7687-9654","authenticated-orcid":false,"given":"Jason A","family":"Tye\u2010Din","sequence":"additional","affiliation":[{"name":"Immunology Division Walter and Eliza Hall Institute Parkville VIC Australia"},{"name":"Department of Medical Biology The University of Melbourne Parkville VIC Australia"},{"name":"Department of Gastroenterology The Royal Melbourne Hospital Parkville VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony D","family":"Kelleher","sequence":"additional","affiliation":[{"name":"Immunovirology and Pathogenesis Program The Kirby Institute UNSW Australia Sydney NSW Australia"},{"name":"St Vincent's Centre for Applied Medical Research St Vincent's Hospital Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"van Bockel","sequence":"additional","affiliation":[{"name":"Immunovirology and Pathogenesis Program The Kirby Institute UNSW Australia Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,1,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2274"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1977"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature22383"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12904"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2011.03842.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0698-713"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3001012"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/73200"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.02.015"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1101526"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2817"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2015.147"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxh065"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1086\/340637"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.3.1151"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0803548"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201344102"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2260"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-04-079863"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.11.7853"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.9.5843"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1175"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00251-002-0508-y"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.10.5729"},{"key":"e_1_2_8_26_1","first-page":"10.33.11","article-title":"Unbiased molecular analysis of T cell receptor expression using template\u2010switch anchored RT\u2010PCR","volume":"10","author":"Quigley MF","year":"2011","journal-title":"Curr Protoc Immunol"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1159\/000019123"}],"container-title":["Clinical &amp; 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