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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2019,7,23]]},"abstract":"<jats:p>B cells play important roles in autoimmune diseases through autoantibody production, cytokine secretion, or antigen presentation to T cells. In most cases, the contribution of B cells as antigen-presenting cells is not well understood. We have studied the autoantibody response against the enzyme transglutaminase 2 (TG2) in celiac disease patients by generating recombinant antibodies from single gut plasma cells reactive with discrete antigen domains and by undertaking proteomic analysis of anti-TG2 serum antibodies. The majority of the cells recognized epitopes in the N-terminal domain of TG2. Antibodies recognizing C-terminal epitopes interfered with TG2 cross-linking activity, and B cells specific for C-terminal epitopes were inefficient at taking up TG2-gluten complexes for presentation to gluten-specific T cells. The bias toward N-terminal epitopes hence reflects efficient T-B collaboration. Production of antibodies against N-terminal epitopes coincided with clinical onset of disease, suggesting that TG2-reactive B cells with certain epitope specificities could be the main antigen-presenting cells for pathogenic, gluten-specific T cells. The link between B cell epitopes, antigen presentation, and disease onset provides insight into the pathogenic mechanisms of a T cell-mediated autoimmune condition.<\/jats:p>","DOI":"10.1073\/pnas.1901561116","type":"journal-article","created":{"date-parts":[[2019,7,8]],"date-time":"2019-07-08T20:25:59Z","timestamp":1562617559000},"page":"15134-15139","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":61,"title":["Efficient T cell\u2013B cell collaboration guides autoantibody epitope bias and onset of celiac disease"],"prefix":"10.1073","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3292-1766","authenticated-orcid":false,"given":"Rasmus","family":"Iversen","sequence":"first","affiliation":[{"name":"KG Jebsen Coeliac Disease Research Centre, University of Oslo, NO-0372 Oslo, Norway;"},{"name":"Department of Immunology, Oslo University Hospital, NO-0372 Oslo, Norway;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bishnudeo","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Immunology, Oslo University Hospital, NO-0372 Oslo, Norway;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorunn","family":"Stamnaes","sequence":"additional","affiliation":[{"name":"KG Jebsen Coeliac Disease Research Centre, University of Oslo, NO-0372 Oslo, Norway;"},{"name":"Department of Immunology, Oslo University Hospital, NO-0372 Oslo, Norway;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6070-1413","authenticated-orcid":false,"given":"Lene S.","family":"H\u00f8ydahl","sequence":"additional","affiliation":[{"name":"KG Jebsen Coeliac Disease Research Centre, University of Oslo, NO-0372 Oslo, Norway;"},{"name":"Department of Immunology, Oslo University Hospital, NO-0372 Oslo, Norway;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Hnida","sequence":"additional","affiliation":[{"name":"Department of Immunology, Oslo University Hospital, NO-0372 Oslo, Norway;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf S.","family":"Neumann","sequence":"additional","affiliation":[{"name":"KG Jebsen Coeliac Disease Research Centre, University of Oslo, NO-0372 Oslo, Norway;"},{"name":"Department of Immunology, Oslo University Hospital, NO-0372 Oslo, Norway;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilma R.","family":"Korponay-Szab\u00f3","sequence":"additional","affiliation":[{"name":"Celiac Disease Center, Heim P\u00e1l National Pediatric Institute, HU-1089 Budapest, Hungary;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Knut E. 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