{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T12:45:48Z","timestamp":1792586748539,"version":"4.5.0"},"reference-count":64,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["7R01DK132583"],"award-info":[{"award-number":["7R01DK132583"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1R21AI193399"],"award-info":[{"award-number":["1R21AI193399"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunological Reviews"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Pancreatic beta cells are active participants in the loss of immune tolerance because their high secretory demand creates exceptional vulnerability to inflammatory exposure, endoplasmic reticulum (ER) stress, calcium dysregulation, and redox imbalance. These conditions can promote enzymatic and nonenzymatic changes in self\u2010proteins, generating post\u2010translationally modified (PTM) antigens and neoepitopes that were absent or poorly represented during immune tolerance. This review integrates the contributions with the broader type 1 diabetes (T1D) field to examine how beta cell stress, transglutaminase\u20102 dependent reactions, peptidyl\u2010arginine deiminase mediated citrullination, oxidative modifications, and post\u2010translational peptide fusion reshape the antigenic landscape. We consider how these products alter antigen presentation and recognition by autoreactive T cells and how an evolving neoepitope repertoire may promote antigenic diversification and epitope spreading. Importantly, clonal recruitment of new determinants must be distinguished from apparent broadening caused by T cell receptor (TCR) cross\u2010reactivity, dual\u2010TCR expression, bystander activation, or tissue redistribution. Defining when modified epitopes arise, which are naturally presented, and which responses contribute to pathogenesis could improve biomarker development, patient stratification, and therapeutic strategies designed to reduce beta cell stress, thus enhancing survival and identity maintenance, while restoring immune tolerance.<\/jats:p>","DOI":"10.1111\/imr.70183","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T09:09:43Z","timestamp":1791364183000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Beta Cell Stress to Epitope Diversification: Post\u2010Translationally Modified Antigens in Type\u00a01 Diabetes"],"prefix":"10.1111","volume":"343","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9247-2787","authenticated-orcid":false,"given":"Megan L.","family":"Proffer","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology Indiana University School of 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