{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:56:49Z","timestamp":1787839009252,"version":"build-2784847793"},"reference-count":39,"publisher":"National Academy of Sciences","issue":"26","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006095","name":"South-Eastern Norway Regional Health Authority","doi-asserted-by":"crossref","award":["2022040"],"award-info":[{"award-number":["2022040"]}],"id":[{"id":"10.13039\/501100006095","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005416","name":"Research Council of Norway","doi-asserted-by":"crossref","award":["287234"],"award-info":[{"award-number":["287234"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,6,30]]},"abstract":"<jats:p>\n                    Polymorphisms of human leukocyte antigen (HLA) genes confer risks for human diseases. Predisposing effects related to T cell receptor (TCR) recognition of peptide\u2013HLA can be selection of TCR repertoire and\/or preferential presentation of disease-driving epitopes. In celiac disease (CeD), HLA-DQ2.5 predisposes by presenting gluten peptides to CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells that typically employ stereotyped TCRs. Here, we analyzed whether genetic variants within the HLA and TR loci shape the naive TCR repertoire. We sequenced the \u03b1\u03b2 TCR repertoires of naive CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells of 103 CeD subjects and 103 controls and performed gene usage quantitative trait loci analyses. The naive CD4\n                    <jats:sup>+<\/jats:sup>\n                    TCR repertoire was significantly affected by TRA, TRB, and in particular HLA polymorphisms. The presence of HLA-DQ2.5 influenced the TCR repertoire, resulting in significant enrichment of TCR genes being involved in recognition of gluten epitopes in the repertoires of CeD subjects versus controls. HLA thus affects disease risk by selection of a disease-relevant TCR repertoire.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2520636123","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T17:38:56Z","timestamp":1782495536000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1,"title":["A predisposing effect of HLA class II genes in celiac disease by skewing the naive CD4\n                    <sup>+<\/sup>\n                    T cell receptor repertoire"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8343-2842","authenticated-orcid":false,"given":"Ida","family":"Lindeman","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01xtthb56","id-type":"ROR","asserted-by":"publisher"}],"name":"Norwegian Coeliac Disease Research Centre, University of Oslo","place":["Oslo, Norway"]},{"id":[{"id":"https:\/\/ror.org\/00j9c2840","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Immunology, Oslo University Hospital\u2013Rikshospitalet","place":["Oslo, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6799-8751","authenticated-orcid":false,"given":"Aengus","family":"Officer","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01xtthb56","id-type":"ROR","asserted-by":"publisher"}],"name":"Norwegian Coeliac Disease Research Centre, University of Oslo","place":["Oslo, Norway"]},{"id":[{"id":"https:\/\/ror.org\/01xtthb56","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Clinical Medicine, University of Oslo","place":["Oslo, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiva","family":"Dahal-Koirala","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00j9c2840","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Immunology, Oslo University Hospital\u2013Rikshospitalet","place":["Oslo, Norway"]},{"id":[{"id":"https:\/\/ror.org\/01xtthb56","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Clinical Medicine, University of Oslo","place":["Oslo, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise F.","family":"Risnes","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01xtthb56","id-type":"ROR","asserted-by":"publisher"}],"name":"Norwegian Coeliac Disease Research Centre, University of Oslo","place":["Oslo, Norway"]},{"id":[{"id":"https:\/\/ror.org\/00j9c2840","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Gastroenterology, Oslo University Hospital\u2013Rikshospitalet","place":["Oslo, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8057-3882","authenticated-orcid":false,"given":"Rebecka","family":"Hjort","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05xg72x27","id-type":"ROR","asserted-by":"publisher"}],"name":"HUNT Research Centre, Department of Public Health and Nursing, Norwegian University of Science and Technology","place":["Levanger, Norway"]},{"id":[{"id":"https:\/\/ror.org\/05xg72x27","id-type":"ROR","asserted-by":"publisher"}],"name":"HUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology","place":["Trondheim, Norway"]},{"id":[{"id":"https:\/\/ror.org\/029nzwk08","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Levanger Hospital, Nord-Tr\u00f8ndelag Hospital Trust","place":["Levanger, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1713-5545","authenticated-orcid":false,"given":"Knut E. A.","family":"Lundin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01xtthb56","id-type":"ROR","asserted-by":"publisher"}],"name":"Norwegian Coeliac Disease Research Centre, University of Oslo","place":["Oslo, Norway"]},{"id":[{"id":"https:\/\/ror.org\/01xtthb56","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Clinical Medicine, University of Oslo","place":["Oslo, Norway"]},{"id":[{"id":"https:\/\/ror.org\/00j9c2840","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Gastroenterology, Oslo University Hospital\u2013Rikshospitalet","place":["Oslo, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6005-0729","authenticated-orcid":false,"given":"Eivind","family":"Ness-Jensen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05xg72x27","id-type":"ROR","asserted-by":"publisher"}],"name":"HUNT Research Centre, Department of Public Health and Nursing, Norwegian University of Science and Technology","place":["Levanger, Norway"]},{"id":[{"id":"https:\/\/ror.org\/05xg72x27","id-type":"ROR","asserted-by":"publisher"}],"name":"HUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology","place":["Trondheim, Norway"]},{"id":[{"id":"https:\/\/ror.org\/029nzwk08","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Levanger Hospital, Nord-Tr\u00f8ndelag Hospital Trust","place":["Levanger, Norway"]},{"id":[{"id":"https:\/\/ror.org\/00m8d6786","id-type":"ROR","asserted-by":"publisher"}],"name":"Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet and Karolinska University Hospital","place":["Stockholm, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7248-8787","authenticated-orcid":false,"given":"Corey T.","family":"Watson","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01ckdn478","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Genetics, School of Medicine, University of Louisville","place":["Louisville"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8860-704X","authenticated-orcid":false,"given":"Ludvig M.","family":"Sollid","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01xtthb56","id-type":"ROR","asserted-by":"publisher"}],"name":"Norwegian Coeliac Disease Research Centre, University of Oslo","place":["Oslo, Norway"]},{"id":[{"id":"https:\/\/ror.org\/00j9c2840","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Immunology, Oslo University Hospital\u2013Rikshospitalet","place":["Oslo, Norway"]},{"id":[{"id":"https:\/\/ror.org\/01xtthb56","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Clinical Medicine, University of Oslo","place":["Oslo, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,6,26]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81110-1"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2014.08.005"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3502"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.372"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-36120-z"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41435-021-00145-5"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.143"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0198-8859(97)00024-4"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3625"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.73475"},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","unstructured":"L. Zhang HLA-DQB1*03:01 strongly affects age of onset of type 1 narcolepsy independently of DQA1 and ethnicity. medRxiv [Preprint] (2025). https:\/\/doi.org\/10.1101\/2025.06.14.25328971 (Accessed 3 August 2025).","DOI":"10.1101\/2025.06.14.25328971"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02064"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0140815"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01032-z"},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","unstructured":"H. J. Zahid Large-scale statistical mapping of T-cell receptor \u03b2 sequences to human leukocyte antigens. bioRxiv [Preprint] (2024). https:\/\/doi.org\/10.1101\/2024.04.01.587617 (Accessed 09 May 2024).","DOI":"10.1101\/2024.04.01.587617"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathmechdis-031521-032634"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2021-326257"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.639672"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2024-333886"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2023-077131"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyac095"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.01.026"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.107735"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.179.5.1707"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.7.1011"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-005-0111-z"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1086\/321297"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2016.07.010"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1500161"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2817"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1009254"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyae073"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1002877"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI98819"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu138"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv359"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae979"},{"key":"e_1_3_4_38_2","unstructured":"I. Lindeman Genetic control of naive T cell receptor gene usage. Federated European Genome-Phenome Archive (EGA) Norway. https:\/\/ega-archive.org\/studies\/EGAS50000001882. Deposited 8 June 2026."},{"key":"e_1_3_4_39_2","unstructured":"I. Lindeman A. Officer C. Watson L. M. Sollid A predisposing effect of HLA class II genes in celiac disease by skewing the naive CD4+ T-cell receptor repertoire (scripts for data analysis). Zenodo. https:\/\/doi.org\/10.5281\/zenodo.20393232. Deposited 18 June 2026."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2520636123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T17:39:21Z","timestamp":1782495561000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2520636123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,26]]},"references-count":39,"journal-issue":{"issue":"26","published-print":{"date-parts":[[2026,6,30]]}},"alternative-id":["10.1073\/pnas.2520636123"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2520636123","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,26]]},"assertion":[{"value":"2025-08-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2520636123"}}