{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T20:34:10Z","timestamp":1791578050112,"version":"4.3.4"},"reference-count":13,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T00:00:00Z","timestamp":1615852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007793","name":"Stiftelsen Kristian Gerhard Jebsen","doi-asserted-by":"publisher","award":["SKGJ-MED-017"],"award-info":[{"award-number":["SKGJ-MED-017"]}],"id":[{"id":"10.13039\/100007793","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005416","name":"Norges Forskningsr\u00e5d","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Chronic inflammation of the small intestine in celiac disease is driven by activation of CD4+ T cells that recognize gluten peptides presented by disease-associated HLA-DQ molecules. We have performed direct cell cloning of duodenal biopsies from five untreated and one refractory celiac disease patients, and three non-celiac disease control subjects in order to assess, in an unbiased fashion, the frequency of gluten-reactive T cells in the disease-affected tissue as well as the antigen fine specificity of the responding T cells. From the biopsies of active disease lesions of five patients, 19 T-cell clones were found to be gluten-reactive out of total 1,379 clones tested. This gave an average of 1.4% (range 0.7% - 1.9%) of gluten-reactive T cells in lamina propria of active celiac lesions. Interestingly, also the patient with refractory celiac disease had gluten-reactive T cell clones in the lamina propria (5\/273; 1.8%). In comparison, we found no gluten-reactive T cells in any of the total 984 T-cell clones screened from biopsies from three disease control donors. Around two thirds of the gluten-reactive clones were reactive to a panel of peptides representing known gluten T-cell epitopes, of which two thirds were reactive to the immunodominant DQ2.5-glia-\u03b11\/DQ2.5-glia-\u03b12 and DQ2.5-glia-\u03c91\/DQ2.5-glia-\u03c92 epitopes. This study shows that gluten-reactive T cells in the inflamed duodenal tissue are prevalent in the active disease lesion, and that many of these T cells are reactive to T-cell epitopes that are not yet characterized. Knowledge of the prevalence and epitope specificity of gluten-specific T cells is a prerequisite for therapeutic efforts that target disease-specific T cells in celiac disease.<\/jats:p>","DOI":"10.3389\/fimmu.2021.646163","type":"journal-article","created":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T04:49:25Z","timestamp":1615870165000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Frequency of Gluten-Reactive T Cells in Active Celiac Lesions Estimated by Direct Cell Cloning"],"prefix":"10.3389","volume":"12","author":[{"given":"Shuo-Wang","family":"Qiao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiva","family":"Dahal-Koirala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linn M.","family":"Eggesb\u00f8","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Knut E. A.","family":"Lundin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludvig M.","family":"Sollid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s00251-019-01141-w","article-title":"Update 2020: nomenclature and listing of celiac disease-relevant gluten epitopes recognized by CD4+ T cells","volume":"72","author":"Sollid","year":"2020","journal-title":"Immunogenetics"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3083.1997.d01-93.x-i2","article-title":"Gliadin specific, HLA DQ2-restricted T cells are commonly found in small intestinal biopsies from coeliac disease patients, but not from controls","volume":"46","author":"Molberg","year":"1997","journal-title":"Scand J Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2017.11.006","article-title":"HLA-DQ\u2212gluten tetramer blood test accurately identifies patients with and without celiac disease in absence of gluten consumption","volume":"154","author":"Sarna","year":"2018","journal-title":"Gastroenterology"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.fm.2006.07.004","article-title":"Chemistry of gluten proteins","volume":"24","author":"Wieser","year":"2007","journal-title":"Food Microbiol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20012028","article-title":"Specificity of tissue transglutaminase explains cereal toxicity in celiac disease","volume":"195","author":"Vader","year":"2002","journal-title":"J Exp Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1084\/jem.191.4.603","article-title":"The intestinal T cell response to \u03b1-gliadin in adult celiac disease is focused on a single deamidated glutamine targeted by tissue transglutaminase","volume":"191","author":"Arentz-Hansen","year":"2000","journal-title":"J Exp Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.1.254","article-title":"Refining the rules of gliadin T cell epitope binding to the disease-associated DQ2 molecule in celiac disease: Importance of proline spacing and glutamine deamidation","volume":"175","author":"Qiao","year":"2005","journal-title":"J Immunol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"41ra51","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 Trans Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.07.013","article-title":"Consistency in polyclonal T-cell responses to gluten between children and adults with celiac disease","volume":"149","author":"Hardy","year":"2015","journal-title":"Gastroenterology"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201343382","article-title":"Direct cloning and tetramer staining to measure the frequency of intestinal gluten-reactive T cells in celiac disease","volume":"43","author":"Bodd","year":"2013","journal-title":"Eur J Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1172\/JCI98819","article-title":"and Sollid, L.M., Disease-driving CD4+ T cell clonotypes persist for decades in celiac disease","volume":"128","author":"Risnes","year":"2018","journal-title":"J Clin Invest"},{"key":"B12","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1177\/2050640619844125","article-title":"European Society for the Study of Coeliac Disease (ESsCD) guideline for coeliac disease and other gluten-related disorders","volume":"7","author":"Al-Toma","year":"2019","journal-title":"United European Gastroenterol J"},{"key":"B13","doi-asserted-by":"crossref","DOI":"10.1385\/1-59259-082-9:105","article-title":"Studies of gliadin-specific T cells in celiac disease","volume-title":"Celiac Disease - Methods and Protocols","author":"Molberg","year":"2000"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.646163\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T04:49:28Z","timestamp":1615870168000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.646163\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,16]]},"references-count":13,"alternative-id":["10.3389\/fimmu.2021.646163"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.646163","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,16]]},"article-number":"646163"}}