{"doi":"10.2337/db19-0620","title":"Hybrid Insulin Peptides Are Recognized by Human T Cells in the Context of DRB1*04:01","abstract":"T cells isolated from the pancreatic infiltrates of nonobese diabetic mice have been shown to recognize epitopes formed by the covalent cross-linking of proinsulin and secretory granule peptides. Formation of such hybrid insulin peptides (HIPs) was confirmed through mass spectrometry, and responses to HIPs were observed among the islet-infiltrating T cells of pancreatic organ donors and in the peripheral blood of individuals with type 1 diabetes (T1D). However, questions remain about the prevalence of HIP-specific T cells in humans, the sequences they recognize, and their role in disease. We identified six novel HIPs that are recognized in the context of DRB1*04:01, discovered by using a library of theoretical HIP sequences derived from insulin fragments covalently linked to one another or to fragments of secretory granule proteins or other islet-derived proteins. We demonstrate that T cells that recognize these HIPs are detectable in the peripheral blood of subjects with T1D and exhibit an effector memory phenotype. HIP-reactive T-cell clones produced Th1-associated cytokines and proliferated in response to human islet preparations. These results support the relevance of HIPs in human disease, further establishing a novel posttranslational modification that may contribute to the loss of peripheral tolerance in T1D.","journal":"Diabetes","year":2020,"id":67300,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":47,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9514,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":357605,"name":"Perrin Guyer","orcid":null,"position":1,"is_corresponding":false},{"id":356451,"name":"Thomas Delong","orcid":"0000-0002-3199-9385","position":2,"is_corresponding":false},{"id":357606,"name":"Mylinh Dang","orcid":null,"position":3,"is_corresponding":false},{"id":281008,"name":"I‐Ting Chow","orcid":"0000-0001-7278-8157","position":4,"is_corresponding":false},{"id":271012,"name":"Cate Speake","orcid":"0000-0003-1480-4272","position":5,"is_corresponding":false},{"id":71415,"name":"Carla J. Greenbaum","orcid":"0000-0003-4451-9800","position":6,"is_corresponding":false},{"id":281006,"name":"William W. Kwok","orcid":"0000-0003-4843-4599","position":7,"is_corresponding":false},{"id":356452,"name":"Rocky L. Baker","orcid":"0000-0001-8361-8655","position":8,"is_corresponding":false},{"id":356453,"name":"Kathryn Haskins","orcid":"0000-0002-5430-6254","position":9,"is_corresponding":false},{"id":108429,"name":"Eddie A. James","orcid":"0000-0002-7217-5729","position":10,"is_corresponding":false},{"id":357604,"name":"David Arribas-Layton","orcid":null,"position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-18T21:15:12.020735Z","pmid":"32291282","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}