{"doi":"10.3389/fimmu.2022.926650","title":"Insulin B-chain hybrid peptides are agonists for T cells reactive to insulin B:9-23 in autoimmune diabetes","abstract":"Insulin is considered to be a key antigenic target of T cells in Type 1 Diabetes (T1D) and autoimmune diabetes in the NOD mouse with particular focus on the B-chain amino acid sequence B:9-23 as the primary epitope. Our lab previously discovered that hybrid insulin peptides (HIPs), comprised of insulin C-peptide fragments fused to other β-cell granule peptides, are ligands for several pathogenic CD4 T cell clones derived from NOD mice and for autoreactive CD4 T cells from T1D patients. A subset of CD4 T cell clones from our panel react to insulin and B:9-23 but only at high concentrations of antigen. We hypothesized that HIPs might also be formed from insulin B-chain sequences covalently bound to other endogenously cleaved ß-cell proteins. We report here on the identification of a B-chain HIP, termed the 6.3HIP, containing a fragment of B:9-23 joined to an endogenously processed peptide of ProSAAS, as a strong neo-epitope for the insulin-reactive CD4 T cell clone BDC-6.3. Using an I-A g7 tetramer loaded with the 6.3HIP, we demonstrate that T cells reactive to this B-chain HIP can be readily detected in NOD mouse islet infiltrates. This work suggests that some portion of autoreactive T cells stimulated by insulin B:9-23 may be responding to B-chain HIPs as peptide ligands.","journal":"Frontiers in Immunology","year":2022,"id":255667,"datarank":0.7040027246581132,"base_score":3.044522437723423,"endowment":3.044522437723423,"self_citation_contribution":0.4566783656585135,"citation_network_contribution":0.24732435899959967,"self_endowment_contribution":0.4566783656585135,"citer_contribution":0.24732435899959967,"corpus_percentile":null,"corpus_rank":null,"citation_count":20,"citer_count":19,"citers_with_citation_signal":15,"citers_with_endowment":15,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9585,"is_data_producer":true,"deposit_databanks":{"figshare":["10.6084/m9.figshare.20092523.v1"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":394806,"name":"James E. DiLisio","orcid":"0000-0001-9216-0375","position":1,"is_corresponding":false},{"id":866850,"name":"Gene Barbour","orcid":null,"position":2,"is_corresponding":false},{"id":357606,"name":"Mylinh Dang","orcid":null,"position":3,"is_corresponding":false},{"id":699768,"name":"Anita C. Hohenstein","orcid":"0000-0002-3655-6276","position":4,"is_corresponding":false},{"id":369808,"name":"Maki Nakayama","orcid":"0000-0002-0009-3687","position":5,"is_corresponding":false},{"id":356451,"name":"Thomas Delong","orcid":"0000-0002-3199-9385","position":6,"is_corresponding":false},{"id":356452,"name":"Rocky L. Baker","orcid":"0000-0001-8361-8655","position":7,"is_corresponding":false},{"id":356453,"name":"Kathryn Haskins","orcid":"0000-0002-5430-6254","position":8,"is_corresponding":false},{"id":717358,"name":"Janet M. Wenzlau","orcid":null,"position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T00:25:17.224217Z","pmid":"36032090","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":[]}