{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T04:49:47Z","timestamp":1791002987268,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T00:00:00Z","timestamp":1643932800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The pathogenic immune response in celiac disease (CeD) is orchestrated by phenotypically distinct CD4<jats:sup>+<\/jats:sup> T cells that recognize gluten epitopes in the context of disease\u2010associated HLA\u2010DQ allotypes. Cells with the same distinct phenotype, but with elusive specificities, are increased across multiple autoimmune conditions. Here, whether sorting of T cells based on their distinct phenotype (Tphe cells) yields gluten\u2010reactive cells in CeD is tested. The method\u2032s efficiency is benchmarked by parallel isolation of gluten\u2010reactive T cells (Ttet cells), using HLA\u2010DQ:gluten peptide tetramers. From gut biopsies of 12 untreated HLA\u2010DQ2.5<jats:sup>+<\/jats:sup> CeD patients, Ttet<jats:sup>+<\/jats:sup>\/Tphe<jats:sup>+<\/jats:sup>, Ttet<jats:sup>\u2212<\/jats:sup>\/Tphe<jats:sup>+<\/jats:sup>, and Ttet<jats:sup>\u2212<\/jats:sup>\/Tphe<jats:sup>\u2212<\/jats:sup> cells are sorted for single\u2010cell T\u2010cell receptor (TCR)\u2010sequencing (<jats:italic>n<\/jats:italic> = 8) and T\u2010cell clone (TCC)\u2010generation (<jats:italic>n<\/jats:italic> = 5). The generated TCCs are TCR sequenced and tested for their reactivity against deamidated gluten. Gluten\u2010reactivity is observed in 91.2% of Ttet<jats:sup>+<\/jats:sup>\/Tphe<jats:sup>+<\/jats:sup> TCCs, 65.3% of Ttet<jats:sup>\u2212<\/jats:sup>\/Tphe<jats:sup>+<\/jats:sup> TCCs and 0% of Ttet<jats:sup>\u2212<\/jats:sup>\/Tphe<jats:sup>\u2212<\/jats:sup> TCCs. TCR sequencing reveals clonal expansion and sequence sharing across patients, features reflecting antigen\u2010driven responses. The feasibility to isolate antigen\u2010specific CD4<jats:sup>+<\/jats:sup> T cells by the sole use of phenotypic markers in CeD outlines a potential avenue for characterizing disease\u2010driving CD4<jats:sup>+<\/jats:sup> T cells in autoimmune conditions.<\/jats:p>","DOI":"10.1002\/advs.202104766","type":"journal-article","created":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T05:39:45Z","timestamp":1643953185000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Phenotype\u2010Based Isolation of Antigen\u2010Specific CD4<sup>+<\/sup> T Cells in Autoimmunity: A Study of Celiac Disease"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4049-807X","authenticated-orcid":false,"given":"Asbj\u00f8rn","family":"Christophersen","sequence":"first","affiliation":[{"name":"KG Jebsen Coeliac Disease Research Centre University of Oslo  Oslo 0372 Norway"},{"name":"Institute of Clinical Medicine University of Oslo  Oslo 0450 Norway"},{"name":"Department of Rheumatology Dermatology and Infectious Diseases Oslo University Hospital  Oslo 0372 Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0165-5098","authenticated-orcid":false,"given":"Shiva","family":"Dahal\u2010Koirala","sequence":"additional","affiliation":[{"name":"KG Jebsen Coeliac Disease Research Centre University of Oslo  Oslo 0372 Norway"},{"name":"Institute of Clinical Medicine University of Oslo  Oslo 0450 Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark\u00e9ta","family":"Chlubnov\u00e1","sequence":"additional","affiliation":[{"name":"KG Jebsen Coeliac Disease Research Centre University of Oslo  Oslo 0372 Norway"},{"name":"Institute of Clinical Medicine University of Oslo  Oslo 0450 Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0419-2914","authenticated-orcid":false,"given":"J\u00f8rgen","family":"Jahnsen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Akershus University Hospital  L\u00f8renskog 1478 Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1713-5545","authenticated-orcid":false,"given":"Knut E. A.","family":"Lundin","sequence":"additional","affiliation":[{"name":"KG Jebsen Coeliac Disease Research Centre University of Oslo  Oslo 0372 Norway"},{"name":"Institute of Clinical Medicine University of Oslo  Oslo 0450 Norway"},{"name":"Department of Gastroenterology Oslo University Hospital Rikshospitalet  Oslo 0372 Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8860-704X","authenticated-orcid":false,"given":"Ludvig M.","family":"Sollid","sequence":"additional","affiliation":[{"name":"KG Jebsen Coeliac Disease Research Centre University of Oslo  Oslo 0372 Norway"},{"name":"Institute of Clinical Medicine University of Oslo  Oslo 0450 Norway"},{"name":"Department of Immunology Oslo University Hospital  Oslo 0372 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