{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T08:43:39Z","timestamp":1790757819442,"version":"4.1.0"},"reference-count":44,"publisher":"National Academy of Sciences","issue":"6","license":[{"start":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T00:00:00Z","timestamp":1595462400000},"content-version":"vor","delay-in-days":182,"URL":"https:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,2,11]]},"abstract":"<jats:p>\n                    The highly homologous human leukocyte antigen (HLA)-DQ2 molecules, HLA-DQ2.5 and HLA-DQ2.2, are implicated in the pathogenesis of celiac disease (CeD) by presenting gluten peptides to CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells. However, while HLA-DQ2.5 is strongly associated with disease, HLA-DQ2.2 is not, and the molecular basis underpinning this differential disease association is unresolved. We here provide structural evidence for how the single polymorphic residue (HLA-DQ2.5-Tyr22\u03b1 and HLA-DQ2.2-Phe22\u03b1) accounts for HLA-DQ2.2 additionally requiring gluten epitopes possessing a serine at the P3 position of the peptide. In marked contrast to the biased T cell receptor (TCR) usage associated with HLA-DQ2.5\u2013mediated CeD, we demonstrate with extensive single-cell sequencing that a diverse TCR repertoire enables recognition of the immunodominant HLA-DQ2.2-glut-L1 epitope. The crystal structure of two CeD patient-derived TCR in complex with HLA-DQ2.2 and DQ2.2-glut-L1 (PFSEQEQPV) revealed a docking strategy, and associated interatomic contacts, which was notably distinct from the structures of the TCR:HLA-DQ2.5:gliadin epitope complexes. Accordingly, while the molecular surfaces of the antigen-binding clefts of HLA-DQ2.5 and HLA-DQ2.2 are very similar, differences in the nature of the peptides presented translates to differences in responding T cell repertoires and the nature of engagement of the respective antigen-presenting molecules, which ultimately is associated with differing disease penetrance.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1914308117","type":"journal-article","created":{"date-parts":[[2020,1,23]],"date-time":"2020-01-23T21:15:12Z","timestamp":1579814112000},"page":"3063-3073","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":62,"title":["A molecular basis for the T cell response in HLA-DQ2.2 mediated celiac disease"],"prefix":"10.1073","volume":"117","author":[{"given":"Yi Tian","family":"Ting","sequence":"first","affiliation":[{"name":"Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia;"},{"name":"The Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0165-5098","authenticated-orcid":false,"given":"Shiva","family":"Dahal-Koirala","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, 0372 Oslo, Norway;"},{"name":"K. G. Jebsen Centre for Coeliac Disease Research, University of Oslo, 0372 Oslo, Norway;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui Shi Keshia","family":"Kim","sequence":"additional","affiliation":[{"name":"Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia;"},{"name":"The Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0935-8397","authenticated-orcid":false,"given":"Shuo-Wang","family":"Qiao","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, 0372 Oslo, Norway;"},{"name":"K. G. Jebsen Centre for Coeliac Disease Research, University of Oslo, 0372 Oslo, Norway;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf S.","family":"Neumann","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, 0372 Oslo, Norway;"},{"name":"K. G. Jebsen Centre for Coeliac Disease Research, University of Oslo, 0372 Oslo, Norway;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Knut E. A.","family":"Lundin","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, 0372 Oslo, Norway;"},{"name":"K. G. Jebsen Centre for Coeliac Disease Research, University of Oslo, 0372 Oslo, Norway;"},{"name":"Department of Gastroenterology, Oslo University Hospital-Rikshospitalet, 0372 Oslo, Norway;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Petersen","sequence":"additional","affiliation":[{"name":"Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia;"},{"name":"The Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia;"},{"name":"Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, VIC 3800, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugh H.","family":"Reid","sequence":"additional","affiliation":[{"name":"Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia;"},{"name":"The Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia;"},{"name":"Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, VIC 3800, Australia;"}],"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":"Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, 0372 Oslo, Norway;"},{"name":"K. 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Jebsen Centre for Coeliac Disease Research, University of Oslo, 0372 Oslo, Norway;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Rossjohn","sequence":"additional","affiliation":[{"name":"Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia;"},{"name":"The Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia;"},{"name":"Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, VIC 3800, Australia;"},{"name":"Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, CF14 4XN Cardiff, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,1,23]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1146\/annurev-immunol-040210-092915","article-title":"Integration of genetic and immunological insights into a model of celiac disease pathogenesis","volume":"29","author":"Abadie V.","year":"2011","unstructured":"V. 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