{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:56:31Z","timestamp":1790283391895,"version":"4.1.0"},"reference-count":76,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"49","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2023,12,8]]},"abstract":"<jats:p>T cells targeting self-proteins are important mediators in autoimmune diseases. T cells express unique cell-surface receptors (TCRs) that recognize peptides presented by major histocompatibility molecules. TCRs have been identified from blood and pancreatic islets of individuals with type 1 diabetes (T1D). Here, we tracked ~1700 known antigen-specific TCR sequences, islet antigen or viral reactive, in bulk TCR\u03b2 sequencing from longitudinal blood DNA samples in at-risk cases who progressed to T1D, age\/sex\/human leukocyte antigen\u2013matched controls, and a new-onset T1D cohort. Shared and frequent antigen-specific TCR\u03b2 sequences were identified in all three cohorts, and viral sequences were present across all ages. Islet sequences had different patterns of accumulation based upon antigen specificity in the at-risk cases. Furthermore, 73 islet-antigen TCR\u03b2 sequences were present in higher frequencies and numbers in T1D samples relative to controls. The total number of these disease-associated TCR\u03b2 sequences inversely correlated with age at clinical diagnosis, indicating the potential to use disease-relevant TCR sequences as biomarkers in autoimmune disorders.<\/jats:p>","DOI":"10.1126\/sciadv.adj6975","type":"journal-article","created":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T18:58:25Z","timestamp":1702061905000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":23,"title":["Tracking DNA-based antigen-specific T cell receptors during progression to type 1 diabetes"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1955-5850","authenticated-orcid":true,"given":"Angela M.","family":"Mitchell","sequence":"first","affiliation":[{"name":"Barbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO, 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University of Colorado School of Medicine, Aurora, CO, USA."},{"name":"Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3829-9207","authenticated-orcid":true,"given":"Marian J.","family":"Rewers","sequence":"additional","affiliation":[{"name":"Barbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO, USA."},{"name":"Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA."},{"name":"Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0009-3687","authenticated-orcid":true,"given":"Maki","family":"Nakayama","sequence":"additional","affiliation":[{"name":"Barbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO, USA."},{"name":"Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA."},{"name":"Department of Immunology, University of Colorado School of Medicine, Aurora, CO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3766-5244","authenticated-orcid":true,"given":"Aaron W.","family":"Michels","sequence":"additional","affiliation":[{"name":"Barbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO, USA."},{"name":"Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA."},{"name":"Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA."},{"name":"Department of Immunology, University of Colorado School of Medicine, Aurora, CO, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1409155111"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1212755109"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1006874"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3822"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.150070"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60591-7"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-1419"},{"key":"e_1_3_2_9_2","first-page":"38","article-title":"T cell receptor sequencing in autoimmunity","volume":"2","author":"Mitchell A. 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