{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T12:36:59Z","timestamp":1784896619638,"version":"3.55.0"},"reference-count":42,"publisher":"American Society for Clinical Investigation","issue":"17","funder":[{"DOI":"10.13039\/501100006095","name":"South-Eastern Norway Regional Health Authority","doi-asserted-by":"crossref","award":["Grant 2012046"],"award-info":[{"award-number":["Grant 2012046"]}],"id":[{"id":"10.13039\/501100006095","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Research Council of Norway through its Centers of Excellence funding scheme","award":["179573\/V40"],"award-info":[{"award-number":["179573\/V40"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,9,7]]},"abstract":"<jats:p>\n                    Selection of biased T cell receptor (TCR) repertoires across individuals is seen in both infectious diseases and autoimmunity, but the underlying molecular basis leading to these shared repertoires remains unclear. Celiac disease (CD) occurs primarily in HLA-DQ2.5\n                    <jats:sup>+<\/jats:sup>\n                    individuals and is characterized by a CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell response against gluten epitopes dominated by DQ2.5-glia-\u03b11a and DQ2.5-glia-\u03b12. The DQ2.5-glia-\u03b12 response recruits a highly biased TCR repertoire composed of TRAV26-1 paired with TRBV7-2 harboring a semipublic CDR3\u03b2 loop. We aimed to unravel the molecular basis for this signature. By variable gene segment exchange, directed mutagenesis, and cellular T cell activation studies, we found that TRBV7-3 can substitute for TRBV7-2, as both can contain the canonical CDR3\u03b2 loop. Furthermore, we identified a pivotal germline-encoded MHC recognition motif centered on framework residue Y40 in TRAV26-1 engaging both DQB1*02 and the canonical CDR3\u03b2. This allowed prediction of expanded DQ2.5-glia-\u03b12\u2013reactive TCR repertoires, which were confirmed by single-cell sorting and TCR sequencing from CD patient samples. Our data refine our understanding of how HLA-dependent biased TCR repertoires are selected in the periphery due to germline-encoded residues.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.95193","type":"journal-article","created":{"date-parts":[[2017,9,6]],"date-time":"2017-09-06T17:27:40Z","timestamp":1504718860000},"source":"Crossref","is-referenced-by-count":20,"title":["A TCR\u03b1 framework\u2013centered codon shapes a biased T cell repertoire through direct MHC and CDR3\u03b2 interactions"],"prefix":"10.1172","volume":"2","author":[{"given":"Kristin St\u00f8en","family":"Gunnarsen","sequence":"first","affiliation":[{"name":"Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, Oslo, Norway."},{"name":"Department of Biosciences, University of Oslo, Oslo, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lene St\u00f8kken","family":"H\u00f8ydahl","sequence":"additional","affiliation":[{"name":"Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, Oslo, Norway."},{"name":"Department of Biosciences, University of Oslo, Oslo, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise Fremgaard","family":"Risnes","sequence":"additional","affiliation":[{"name":"Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, Oslo, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiva","family":"Dahal-Koirala","sequence":"additional","affiliation":[{"name":"Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, Oslo, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf Stefan","family":"Neumann","sequence":"additional","affiliation":[{"name":"Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, Oslo, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elin","family":"Bergseng","sequence":"additional","affiliation":[{"name":"Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, Oslo, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terje","family":"Frigstad","sequence":"additional","affiliation":[{"name":"Nextera AS, Oslo, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahel","family":"Frick","sequence":"additional","affiliation":[{"name":"Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, Oslo, Norway."},{"name":"Department of Biosciences, University of Oslo, Oslo, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Fleur","family":"du Pr\u00e9","sequence":"additional","affiliation":[{"name":"Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, Oslo, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f8rn","family":"Dalhus","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Oslo University Hospital-Rikshospitalet, Oslo, Norway."},{"name":"Department of Medical Biochemistry, Institute for Clinical Medicine, University of Oslo, Oslo, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Knut E.A.","family":"Lundin","sequence":"additional","affiliation":[{"name":"Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, Oslo, Norway."},{"name":"KG Jebsen Coeliac Disease Research Centre and Department of Immunology, University of Oslo, Oslo, Norway."},{"name":"Department of Gastroenterology, Oslo University Hospital-Rikshospitalet, Oslo, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo-Wang","family":"Qiao","sequence":"additional","affiliation":[{"name":"Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, Oslo, Norway."},{"name":"KG Jebsen Coeliac Disease Research Centre and Department of Immunology, University of Oslo, Oslo, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8860-704X","authenticated-orcid":true,"given":"Ludvig M.","family":"Sollid","sequence":"additional","affiliation":[{"name":"Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, Oslo, Norway."},{"name":"KG Jebsen Coeliac Disease Research Centre and Department of Immunology, University of Oslo, Oslo, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inger","family":"Sandlie","sequence":"additional","affiliation":[{"name":"Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, Oslo, Norway."},{"name":"Department of Biosciences, University of Oslo, Oslo, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5257-8571","authenticated-orcid":true,"given":"Geir \u00c5ge","family":"L\u00f8set","sequence":"additional","affiliation":[{"name":"Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, Oslo, Norway."},{"name":"Department of Biosciences, University of Oslo, Oslo, Norway."},{"name":"Nextera AS, Oslo, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2017,9,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.23.021704.115658"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2260"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/ni.f.219"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3625"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/S1542-3565(05)00532-X"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1126\/science.1074129"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1084\/jem.191.4.603"},{"issue":"41","key":"B8","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3001012","article-title":"Comprehensive, quantitative mapping of T cell epitopes in gluten in celiac disease","volume":"2","author":"Tye-Din","year":"2010","journal-title":"Sci Transl Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/nm0698-713"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1101526"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxt037"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2817"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2008.09.021"},{"key":"B14","doi-asserted-by":"crossref","DOI":"10.1038\/srep01162","article-title":"Chaperone-assisted thermostability engineering of a soluble T cell receptor using phage display","volume":"3","author":"Gunnarsen","year":"2013","journal-title":"Sci Rep"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.9.5727"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.16.1.523"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2016.07.010"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.07.013"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/nature08746"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201445358"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2015.147"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2938"},{"key":"B23","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms11112","article-title":"Individual heritable differences result in unique cell lymphocyte receptor repertoires of na\u00efve and antigen-experienced cells","volume":"7","author":"Rubelt","year":"2016","journal-title":"Nat Commun"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1780"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1500161"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.07.007"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/ni1502"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.01.008"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.05.018"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.10.012"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/nature07812"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.09.013"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.8.5451"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1100255"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.785139"},{"key":"B36","first-page":"105","article-title":"Studies of gliadin-specific T-cells in celiac disease","volume":"41","author":"Molberg","year":"2000","journal-title":"Methods Mol Med"},{"key":"B37","doi-asserted-by":"crossref","DOI":"10.1186\/1472-6750-10-8","article-title":"Periplasmic expression of soluble single chain T cell receptors is rescued by the chaperone FkpA","volume":"10","author":"Gunnarsen","year":"2010","journal-title":"BMC Biotechnol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.9.4861"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/0198-8859(94)00110-C"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830191214"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth858"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0306885101"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/95193\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T13:33:54Z","timestamp":1779197634000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/95193"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,7]]},"references-count":42,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2017,9,7]]},"published-print":{"date-parts":[[2017,9,7]]}},"alternative-id":["10.1172\/jci.insight.95193"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.95193","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,7]]},"article-number":"e95193"}}