{"doi":"10.17615/0f1y-7y80","title":"T-Cell Promiscuity in Autoimmune Diabetes","abstract":"OBJECTIVE—It is well established that the primary mediators of β-cell destruction in type 1 diabetes are T-cells. Nevertheless, the molecular basis for recognition of β-cell–specific epitopes by pathogenic T-cells remains ill defined; we seek to further explore this issue.RESEARCH DESIGN AND METHODS—To determine the properties of β-cell–specific T-cell receptors (TCRs), we characterized the fine specificity, functional and relative binding avidity/affinity, and diabetogenicity of a panel of GAD65-specific CD4+ T-cell clones established from unimmunized 4- and 14-week-old NOD female mice.RESULTS—The majority of GAD65-specific CD4+ T-cells isolated from 4- and 14-week-old NOD female mice were specific for peptides spanning amino acids 217–236 (p217) and 290–309 (p290). Surprisingly, 31% of the T-cell clones prepared from 14-week-old but not younger NOD mice were stimulated with both p217 and p290. These promiscuous T-cell clones recognized the two epitopes when naturally processed and presented, and this dual specificity was mediated by a single TCR. Furthermore, promiscuous T-cell clones demonstrated increased functional avidity and relative TCR binding affinity, which correlated with enhanced islet infiltration on adoptive transfer compared with that of monospecific T-cell clones.CONCLUSIONS—These results indicate that promiscuous recognition contributes to the development of GAD65-specific CD4+ T-cell clones in NOD mice. Furthermore, these findings suggest that T-cell promiscuity reflects a novel form of T-cell avidity maturation.","journal":"UNC Libraries","year":2020,"id":128501,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9601,"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":523078,"name":"J. A. Frelinger","orcid":null,"position":1,"is_corresponding":false},{"id":166853,"name":"B. Wang","orcid":null,"position":2,"is_corresponding":false},{"id":1874,"name":"L. Li","orcid":"0000-0001-6411-6107","position":3,"is_corresponding":false},{"id":540417,"name":"R. Tisch","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:15:38.879956Z","pmid":null,"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":[]}