{"doi":"10.1084/jem.20200701","title":"Altered selection on a single self-ligand promotes susceptibility to organ-specific T cell infiltration","abstract":"For the large array of self-peptide/MHC class II (pMHC-II) complexes displayed in the body, it is unclear whether CD4+ T cell tolerance must be imparted for each individual complex or whether pMHC-II-nonspecific bystander mechanisms are sufficient to confer tolerance by acting broadly on T cells reactive to multiple self-pMHC-II ligands. Here, via reconstitution of T cell-deficient mice, we demonstrate that altered T cell selection on a single prostate-specific self-pMHC-II ligand renders recipient mice susceptible to prostate-specific T cell infiltration. Mechanistically, this self-pMHC-II complex is required for directing antigen-specific cells into the Foxp3+ regulatory T cell lineage but does not induce clonal deletion to a measurable extent. Thus, our data demonstrate that polyclonal T reg cells are unable to functionally compensate for a breach in tolerance to a single self-pMHC-II complex in this setting, revealing vulnerabilities in antigen-nonspecific bystander mechanisms of immune tolerance.","journal":"The Journal of Experimental Medicine","year":2021,"id":199075,"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":0.9572,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":774949,"name":"Dana C. Gilmore","orcid":"0000-0002-0513-3019","position":1,"is_corresponding":false},{"id":774950,"name":"John D. Leonard","orcid":"0000-0002-3202-8062","position":2,"is_corresponding":false},{"id":289000,"name":"Christine H. Miller","orcid":"0000-0003-2176-9516","position":3,"is_corresponding":false},{"id":702553,"name":"Jaime Chao","orcid":"0000-0003-1872-734X","position":4,"is_corresponding":false},{"id":339433,"name":"Matthew T. Walker","orcid":"0000-0002-0921-5812","position":5,"is_corresponding":false},{"id":774951,"name":"Ryan K. Duncombe","orcid":"0000-0001-7414-0987","position":6,"is_corresponding":false},{"id":658415,"name":"Kenneth S. K. Tung","orcid":"0000-0002-9393-0084","position":7,"is_corresponding":false},{"id":563084,"name":"Erin J. Adams","orcid":"0000-0002-6271-8574","position":8,"is_corresponding":false},{"id":289004,"name":"Peter A. Savage","orcid":"0000-0002-2506-7717","position":9,"is_corresponding":false},{"id":289001,"name":"David E. J. Klawon","orcid":"0000-0001-7953-2525","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-18T23:50:36.595945Z","pmid":"33914024","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":[]}