{"doi":"10.1101/2020.12.16.423036","title":"Non-deletional CD8 <sup>+</sup> T cell self-tolerance permits responsiveness but limits tissue damage","abstract":"Abstract Self-specific CD8+ T cells often escape clonal deletion, but the properties and capabilities of such cells in a physiological setting are unclear. We characterized polyclonal CD8 + T cells specific for the melanocyte antigen tyrosinase-related protein 2 (Trp2) in mice that express or lack this enzyme due to deficiency in Dct , which encodes Trp2. The size, phenotype, and gene expression profile of the pre-immune Trp2/K b -specific pool were similar in wild-type (WT) and Dct -deficient ( Dct -/- ) mice. Despite comparable initial responses to Trp2 immunization, WT Trp2/K b -specific cells showed blunted expansion, and scRNAseq revealed WT cells less readily differentiated into a CD25+ proliferative population. Functional self-tolerance clearly emerged when assessing immunopathology: adoptively transferred WT Trp2/K b -specific cells mediated vitiligo much less efficiently. Hence, CD8 + T cell self-specificity is poorly predicted by precursor frequency, phenotype or even initial responsiveness, while deficient activation-induced CD25 expression and other gene expression characteristics may help to identify functionally tolerant cells.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":131959,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9607,"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":427690,"name":"Kristina S. Burrack","orcid":"0000-0002-6931-226X","position":1,"is_corresponding":false},{"id":462102,"name":"Todd P. Knutson","orcid":"0000-0001-8431-9964","position":2,"is_corresponding":false},{"id":586845,"name":"Henrique Borges da Silva","orcid":"0000-0001-9424-3326","position":3,"is_corresponding":false},{"id":586846,"name":"Katharine E. Block","orcid":"0000-0001-9488-3577","position":4,"is_corresponding":false},{"id":587418,"name":"Katie R Stagliano","orcid":null,"position":5,"is_corresponding":false},{"id":587419,"name":"Arthur A. Hurwitz","orcid":null,"position":6,"is_corresponding":false},{"id":586847,"name":"Ross B. Fulton","orcid":"0000-0002-0705-2917","position":7,"is_corresponding":false},{"id":577564,"name":"Kristin R. Renkema","orcid":"0000-0003-4000-3356","position":8,"is_corresponding":false},{"id":235915,"name":"Stephen C. Jameson","orcid":"0000-0001-9137-1146","position":9,"is_corresponding":false},{"id":586844,"name":"Emily N Truckenbrod","orcid":"0000-0002-3819-6307","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-18T23:16:07.542484Z","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":[]}