{"doi":"10.4049/jimmunol.2300303","title":"HLA-DQ8 Supports Development of Insulitis Mediated by Insulin-Reactive Human TCR-Transgenic T Cells in Nonobese Diabetic Mice","abstract":"In an effort to improve HLA-\"humanized\" mouse models for type 1 diabetes (T1D) therapy development, we previously generated directly in the NOD strain CRISPR/Cas9-mediated deletions of various combinations of murine MHC genes. These new models improved upon previously available platforms by retaining β2-microglobulin functionality in FcRn and nonclassical MHC class I formation. As proof of concept, we generated H2-Db/H2-Kd double knockout NOD mice expressing human HLA-A*0201 or HLA-B*3906 class I variants that both supported autoreactive diabetogenic CD8+ T cell responses. In this follow-up work, we now describe the creation of 10 new NOD-based mouse models expressing various combinations of HLA genes with and without chimeric transgenic human TCRs reactive to proinsulin/insulin. The new TCR-transgenic models develop differing levels of insulitis mediated by HLA-DQ8-restricted insulin-reactive T cells. Additionally, these transgenic T cells can transfer insulitis to newly developed NSG mice lacking classical murine MHC molecules, but expressing HLA-DQ8. These new models can be used to test potential therapeutics for a possible capacity to reduce islet infiltration or change the phenotype of T cells expressing type 1 diabetes patient-derived β cell autoantigen-specific TCRs.","journal":"The Journal of Immunology","year":2023,"id":351870,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9571,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1096920,"name":"Adel Misherghi","orcid":"0000-0003-2048-8122","position":1,"is_corresponding":false},{"id":935747,"name":"Jennifer R. Dwyer","orcid":"0000-0002-5893-6026","position":2,"is_corresponding":false},{"id":817596,"name":"Richard S. Maser","orcid":null,"position":3,"is_corresponding":false},{"id":614644,"name":"Elvira Forte","orcid":"0000-0002-5555-9122","position":4,"is_corresponding":false},{"id":813200,"name":"Olivia Bedard","orcid":"0009-0008-7888-1895","position":5,"is_corresponding":false},{"id":397064,"name":"Susanne Sattler","orcid":"0000-0001-9932-4109","position":6,"is_corresponding":false},{"id":251269,"name":"Alberto Pugliese","orcid":"0000-0002-7211-0319","position":7,"is_corresponding":false},{"id":463865,"name":"Laurie G. Landry","orcid":"0000-0002-4064-9109","position":8,"is_corresponding":false},{"id":1096921,"name":"Colleen M. Elso","orcid":"0000-0003-2962-8726","position":9,"is_corresponding":false},{"id":369808,"name":"Maki Nakayama","orcid":"0000-0002-0009-3687","position":10,"is_corresponding":false},{"id":1096922,"name":"Stuart I. Mannering","orcid":"0000-0003-3497-3559","position":11,"is_corresponding":false},{"id":268613,"name":"Nadia Rosenthal","orcid":"0000-0002-7599-7365","position":12,"is_corresponding":false},{"id":312736,"name":"David Serreze","orcid":null,"position":13,"is_corresponding":false},{"id":530417,"name":"Jeremy J. Racine","orcid":"0000-0001-5514-3074","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-19T01:12:45.897709Z","pmid":"37877672","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":[]}