{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:11:48Z","timestamp":1790651508337,"version":"4.1.0"},"reference-count":23,"publisher":"American Diabetes Association","issue":"5","license":[{"start":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T00:00:00Z","timestamp":1706659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI146202-01"],"award-info":[{"award-number":["R01 AI146202-01"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21 AI133059"],"award-info":[{"award-number":["R21 AI133059"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive Diseases","doi-asserted-by":"crossref","award":["R01 DK081166"],"award-info":[{"award-number":["R01 DK081166"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,5,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>Hybrid insulin peptides (HIPs) formed through covalent cross-linking of proinsulin fragments to secretory granule peptides are detectable within murine and human islets. The 2.5HIP (C-peptide\u2013chromogranin A [CgA] HIP), recognized by the diabetogenic BDC-2.5 clone, is a major autoantigen in the nonobese diabetic mouse. However, the relevance of this epitope in human disease is currently unclear. A recent study probed T-cell reactivity toward HIPs in patients with type 1 diabetes, documenting responses in one-third of the patients and isolating several HIP-reactive T-cell clones. In this study, we isolated a novel T-cell clone and showed that it responds vigorously to the human equivalent of the 2.5HIP (designated HIP9). Although the responding patient carried the risk-associated DRB1*04:01\/DQ8 haplotype, the response was restricted by DRB1*11:03 (DR11). HLA class II tetramer staining revealed higher frequencies of HIP9-reactive T cells in individuals with diabetes than in control participants. Furthermore, in DR11+ participants carrying the DRB4 allele, HIP9-reactive T-cell frequencies were higher than observed frequencies for the immunodominant proinsulin 9-28 epitope. Finally, there was a negative correlation between HIP9-reactive T-cell frequency and age at diagnosis. These results provide direct evidence that this C-peptide\u2013CgA HIP is relevant in human type 1 diabetes and suggest a mechanism by which nonrisk HLA haplotypes may contribute to the development of \u03b2-cell autoimmunity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                  <\/jats:sec>","DOI":"10.2337\/db23-0622","type":"journal-article","created":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T16:38:20Z","timestamp":1706719100000},"page":"743-750","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":13,"title":["An Insulin-Chromogranin A Hybrid Peptide Activates DR11-Restricted T Cells in Human Type 1 Diabetes"],"prefix":"10.2337","volume":"73","author":[{"given":"A\u00efsha","family":"Callebaut","sequence":"first","affiliation":[{"name":"1Center for Translational Immunology, Benaroya Research Institute, Seattle, WA"},{"name":"2Laboratory of Clinical and Experimental Endocrinology, Catholic University of Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perrin","family":"Guyer","sequence":"additional","affiliation":[{"name":"1Center for Translational Immunology, Benaroya Research Institute, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocky L.","family":"Baker","sequence":"additional","affiliation":[{"name":"3Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joylynn B.","family":"Gallegos","sequence":"additional","affiliation":[{"name":"3Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO"},{"name":"4Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita 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