{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T15:56:52Z","timestamp":1790611012663,"version":"4.1.0"},"posted":{"date-parts":[[2026,9,24]]},"group-title":"Immunology","reference-count":45,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Type 1 diabetes (T1D) is mediated by autoreactive CD4 T cells that recognize pancreatic \u03b2-cell antigens MHC class II molecules. The B-chain of insulin is thought to be a primary autoantigen although native peptide sequences from the B-chain bind weakly to disease-associated MHC risk alleles. Hybrid Insulin Peptides (HIPs), consist of proinsulin fragments fused with peptides from other \u03b2-cell proteins, and may endow B-chain peptides with C-terminal acid residues that allow strong binding to MHC risk alleles and subsequent stimulation of autoreactive T cells. Here we applied a high-throughput cell-based screening platform with Signaling and Antigen-presenting Bifunctional Receptors (SABRs) to interrogate a theoretical library of insulin B-chain HIPs against clonally expanded CD4 T cell receptors from NOD mouse islets. We identified a previously undescribed HIP containing a fragment of insulin B-chain combined with a calreticulin-derived peptide. I-A\n                  <jats:sup>g<\/jats:sup>\n                  <jats:sup>7<\/jats:sup>\n                  tetramers loaded with the InsB\/Calr HIP bind to T cell clones as well as islet-infiltrating CD4 T cells and CD4 T cells from a recent-onset HLA-DQ2 T1D donor reacted exclusively to the InsB\/Calr HIP. Collectively, these results demonstrate that insulin B-chain-derived peptides can undergo post-translational modification through HIP formation to generate neoepitopes with increased antigenicity, and underscore the utility of cell-based screening for identifying disease-relevant neoepitopes in T1D.\n                <\/jats:p>","DOI":"10.64898\/2026.09.16.752211","type":"posted-content","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T18:25:16Z","timestamp":1790274316000},"source":"Crossref","is-referenced-by-count":0,"title":["Cell-based epitope screen identifies a novel B chain-derived Hybrid Insulin Peptide recognized by human and mouse autoreactive CD4 T cells"],"prefix":"10.64898","author":[{"given":"James E.","family":"DiLisio","sequence":"first","affiliation":[{"name":"Department of Immunology and Microbiology, School of Medicine, University of Colorado, Aurora, CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M.","family":"Zdinak","sequence":"additional","affiliation":[{"name":"Department of Immunology, Department of Computational and Systems Biology, Center for Systems Immunology, University of Pittsburgh, Pittsburgh, PA USA"},{"name":"Graduate Program in Microbiology and Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nishtha","family":"Trivedi","sequence":"additional","affiliation":[{"name":"Department of Immunology, Department of Computational and Systems Biology, Center for Systems Immunology, University of Pittsburgh, Pittsburgh, PA USA"},{"name":"Graduate Program in Integrative Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet M","family":"Wenzlau","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, School of Medicine, University of Colorado, Aurora, CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita C.","family":"Hohenstein","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, School of Medicine, University of Colorado, Aurora, CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joylynn","family":"Gallegos","sequence":"additional","affiliation":[{"name":"Barbara Davis Center, School of Medicine, University of Colorado, Aurora, CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Gottlieb","sequence":"additional","affiliation":[{"name":"Barbara Davis Center, School of Medicine, University of Colorado, Aurora, CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Haskins","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, School of Medicine, University of Colorado, Aurora, CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocky L.","family":"Baker","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, School of Medicine, University of Colorado, Aurora, CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alok V.","family":"Joglekar","sequence":"additional","affiliation":[{"name":"Department of Immunology, Department of Computational and Systems Biology, Center for Systems Immunology, University of Pittsburgh, Pittsburgh, PA 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