{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T05:51:02Z","timestamp":1784958662187,"version":"3.55.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T00:00:00Z","timestamp":1448928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Autoantibodies specific for the enzyme transglutaminase 2 (TG2) are a hallmark of the gluten-sensitive enteropathy celiac disease. Production of the Abs is strictly dependent on exposure to dietary gluten proteins, thus raising the question how a foreign Ag (gluten) can induce an autoimmune response. It has been suggested that TG2-reactive B cells are activated by gluten-reactive T cells following receptor-mediated uptake of TG2\u2013gluten complexes. In this study, we propose a revised model that is based on the ability of the BCR to serve as a substrate to TG2 and become cross-linked to gluten-derived peptides. We show that TG2-specific IgD molecules are preferred in the reaction and that binding of TG2 via a common epitope targeted by cells using the IgH variable gene segment (IGHV)5\u201351 results in more efficient cross-linking. Based on these findings we hypothesize that IgD-expressing B cells using IGHV5\u201351 are preferentially activated, and we suggest that this property can explain the previously reported low number of somatic mutations as well as the overrepresentation of IGHV5\u201351 among TG2-specific plasma cells in the celiac lesion. The model also couples gluten peptide uptake by TG2-reactive B cells directly to peptide deamidation, which is necessary for the activation of gluten-reactive T cells. It thereby provides a link between gluten deamidation, T cell activation, and the production of TG2-specific Abs. These are all key events in the development of celiac disease, and by connecting them the model may explain why the same enzyme that catalyzes gluten deamidation is also an autoantigen, something that is hardly coincidental.<\/jats:p>","DOI":"10.4049\/jimmunol.1501363","type":"journal-article","created":{"date-parts":[[2015,10,27]],"date-time":"2015-10-27T02:13:34Z","timestamp":1445912014000},"page":"5159-5168","source":"Crossref","is-referenced-by-count":36,"title":["Igs as Substrates for Transglutaminase 2: Implications for Autoantibody Production in Celiac Disease"],"prefix":"10.1093","volume":"195","author":[{"given":"Rasmus","family":"Iversen","sequence":"first","affiliation":[{"name":"Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital , N-0372 Oslo ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9231-643X","authenticated-orcid":false,"given":"M","family":"Fleur du Pr\u00e9","sequence":"additional","affiliation":[{"name":"Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital , N-0372 Oslo ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Di Niro","sequence":"additional","affiliation":[{"name":"Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital , N-0372 Oslo ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludvig M","family":"Sollid","sequence":"additional","affiliation":[{"name":"Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital , N-0372 Oslo ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,12,1]]},"reference":[{"key":"2025030704260312800_r1","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/nri885","article-title":"Coeliac disease: dissecting a complex inflammatory disorder","volume":"2","author":"Sollid","year":"2002","journal-title":"Nat. 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