{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:54:53Z","timestamp":1792814093086,"version":"4.5.0"},"reference-count":76,"publisher":"American Society for Clinical Investigation","issue":"15","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":62,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Netherlands Organization for Scientific Research","award":["452181214"],"award-info":[{"award-number":["452181214"]}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["2U19AI057229"],"award-info":[{"award-number":["2U19AI057229"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,10]]},"abstract":"<jats:p>\n                    Inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn\u2019s disease (CD), is marked by chronic intestinal inflammation and dysregulated immunity. Although UC and CD affect different areas of the gastrointestinal tract, both diseases share aberrant CD4\n                    <jats:sup>+<\/jats:sup>\n                    memory T cell responses, with HLA-DRB1 as a major genetic risk factor. HLA-DRB1 encodes MHC class II molecules that influence the CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell receptor (TCR) repertoire, yet how these genotypes shape TCR specificity in IBD remains unclear. Here, we genotyped HLA-DRB1 and profiled 3.13 million TCR\u03b2 sequences from circulating memory CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells in 33 IBD patients (20 UC, 13 CD) and 14 healthy controls. Using the GLIPH2 algorithm, we distilled 468,441 candidates based on CDR3 amino acid motifs into 440 high-confidence TCR specificity groups significantly enriched among individuals sharing HLA-DRB1 alleles. Notably, 5 specificity groups were IBD-enriched and were shared between UC and CD, suggesting common antigen targets in both diseases. We also observed increased frequencies of clonally expanded cytotoxic\n                    <jats:italic>\n                      GZMB\n                      <jats:sup>+<\/jats:sup>\n                      PRF1\n                      <jats:sup>+<\/jats:sup>\n                    <\/jats:italic>\n                    memory CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells and KIR\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in a subset of risk-allele carriers with IBD. These findings elucidate distinct, HLA-linked TCR specificity groups in IBD and provide mechanistic insights that may advance antigen discovery and personalized medicine.\n                  <\/jats:p>\n                  <jats:p\/>\n                  <jats:p>Crohn's disease and ulcerative colitis patients share patterns in their immune cells, suggesting both conditions may be driven by some of the same unknown triggers.<\/jats:p>","DOI":"10.1172\/jci.insight.195354","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T16:00:32Z","timestamp":1781020832000},"source":"Crossref","is-referenced-by-count":2,"title":["Shared CD4+ T cell receptor specificity groups in Crohn\u2019s disease and ulcerative colitis"],"prefix":"10.1172","volume":"11","author":[{"given":"Joshua E.","family":"Chan","sequence":"first","affiliation":[{"name":"Institute of Immunity, Transplantation and Infection, and"},{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azam","family":"Mohsin","sequence":"additional","affiliation":[{"name":"Institute of Immunity, Transplantation and Infection, and"},{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Krijgsman","sequence":"additional","affiliation":[{"name":"Department of Immunology, Leiden University Medical Center, Leiden, Zuid-Holland, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciska","family":"Lindelauf","sequence":"additional","affiliation":[{"name":"Department of Immunology, Leiden University Medical Center, Leiden, Zuid-Holland, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghui","family":"Mu","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianna","family":"Cavalla","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology & Hepatology, Stanford University School of Medicine, Stanford, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuhuai","family":"Ji","sequence":"additional","affiliation":[{"name":"Human Immune Monitoring Center, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E.","family":"Streett","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology & Hepatology, Stanford University School of Medicine, Stanford, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9339-8430","authenticated-orcid":true,"given":"Vincent","family":"van Unen","sequence":"additional","affiliation":[{"name":"Institute of Immunity, Transplantation and Infection, and"},{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA."},{"name":"Department of Immunology, Leiden University Medical Center, Leiden, Zuid-Holland, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark M.","family":"Davis","sequence":"additional","affiliation":[{"name":"Institute of Immunity, Transplantation and Infection, and"},{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA."},{"name":"Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"key":"B1","unstructured":"Centers for Disease Control and Prevention. 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