{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:20:01Z","timestamp":1792513201647,"version":"4.5.0"},"reference-count":43,"publisher":"Rockefeller University Press","issue":"4","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2000,2,21]]},"abstract":"<jats:p>The great majority of patients that are intolerant of wheat gluten protein due to celiac disease (CD) are human histocompatibility leukocyte antigen (HLA)-DQ2+, and the remaining few normally express HLA-DQ8. These two class II molecules are chiefly responsible for the presentation of gluten peptides to the gluten-specific T cells that are found only in the gut of CD patients but not of controls. Interestingly, tissue transglutaminase (tTG)-mediated deamidation of gliadin plays an important role in recognition of this food antigen by intestinal T cells. Here we have used recombinant antigens to demonstrate that the intestinal T cell response to \u03b1-gliadin in adult CD is focused on two immunodominant, DQ2-restricted peptides that overlap by a seven-residue fragment of gliadin. We show that tTG converts a glutamine residue within this fragment into glutamic acid and that this process is critical for T cell recognition. Gluten-specific T cell lines from 16 different adult patients all responded to one or both of these deamidated peptides, indicating that these epitopes are highly relevant to disease pathology. Binding studies showed that the deamidated peptides displayed an increased affinity for DQ2, a molecule known to preferentially bind peptides containing negatively charged residues. Interestingly, the modified glutamine is accommodated in different pockets of DQ2 for the different epitopes. These results suggest modifications of anchor residues that lead to an improved affinity for major histocompatibility complex (MHC), and altered conformation of the peptide\u2013MHC complex may be a critical factor leading to T cell responses to gliadin and the oral intolerance of gluten found in CD.<\/jats:p>","DOI":"10.1084\/jem.191.4.603","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T12:48:33Z","timestamp":1027687713000},"page":"603-612","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":541,"title":["The Intestinal T Cell Response to \u03b1-Gliadin in Adult Celiac Disease Is Focused on a Single Deamidated Glutamine Targeted by Tissue Transglutaminase"],"prefix":"10.1084","volume":"191","author":[{"given":"Helene","family":"Arentz-Hansen","sequence":"first","affiliation":[{"name":"aFrom the Institute of Immunology, Rikshospitalet, University of Oslo, N-0027 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"K\u00f6rner","sequence":"additional","affiliation":[{"name":"bDepartment of Molecular Biology, Odense University, DK-5230 Odense M, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d8yvind","family":"Molberg","sequence":"additional","affiliation":[{"name":"aFrom the Institute of Immunology, Rikshospitalet, University of Oslo, N-0027 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanne","family":"Quarsten","sequence":"additional","affiliation":[{"name":"aFrom the Institute of Immunology, Rikshospitalet, University of Oslo, N-0027 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willemijn","family":"Vader","sequence":"additional","affiliation":[{"name":"dDepartment of Immunohaematology and Blood Bank, Leiden University Hospital, 2300 RC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne M.C.","family":"Kooy","sequence":"additional","affiliation":[{"name":"dDepartment of Immunohaematology and Blood Bank, Leiden University Hospital, 2300 RC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Knut E.A.","family":"Lundin","sequence":"additional","affiliation":[{"name":"aFrom the Institute of Immunology, Rikshospitalet, University of Oslo, N-0027 Oslo, Norway"},{"name":"cDepartment of Gastroenterology, Ullevaal Hospital, 0407 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frits","family":"Koning","sequence":"additional","affiliation":[{"name":"dDepartment of Immunohaematology and Blood Bank, Leiden University Hospital, 2300 RC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Roepstorff","sequence":"additional","affiliation":[{"name":"bDepartment of Molecular Biology, Odense University, DK-5230 Odense M, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludvig M.","family":"Sollid","sequence":"additional","affiliation":[{"name":"aFrom the Institute of Immunology, Rikshospitalet, University of Oslo, N-0027 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen N.","family":"McAdam","sequence":"additional","affiliation":[{"name":"aFrom the Institute of Immunology, Rikshospitalet, University of Oslo, N-0027 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2000,2,21]]},"reference":[{"key":"2023072509091247600_R1","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1084\/jem.169.1.345","article-title":"Evidence for a primary association of celiac disease to a particular HLA-DQ \u03b1\/\u03b2 heterodimer","volume":"169","author":"Sollid","year":"1989","journal-title":"J. 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J."},{"key":"2023072509091247600_R41","doi-asserted-by":"crossref","first-page":"2663","DOI":"10.4049\/jimmunol.147.8.2663","article-title":"On the interaction of promiscuous antigenic peptides with different DR alleles. Identification of common structural motifs","volume":"147","author":"O'Sullivan","year":"1991","journal-title":"J. Immunol."},{"key":"2023072509091247600_R42","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/0092-8674(93)90306-B","article-title":"Promiscuous and allele-specific anchors in HLA-DR-binding peptides","volume":"74","author":"Hammer","year":"1993","journal-title":"Cell."},{"key":"2023072509091247600_R43","doi-asserted-by":"crossref","first-page":"3163","DOI":"10.4049\/jimmunol.151.6.3163","article-title":"HLA DR4w4-binding motifs illustrate the biochemical basis of degeneracy and specificity in peptide-DR interactions","volume":"151","author":"Sette","year":"1993","journal-title":"J. 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