{"doi":"10.4049/jimmunol.163.2.689","title":"Negative Selection of T Cells Occurs Throughout Thymic Development","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Thymic positive and negative selections govern the development of a self-MHC-reactive, yet self-tolerant, T cell repertoire. Whether these processes occur independently or sequentially remains controversial. To investigate these issues, we have employed tetrameric peptide-MHC complexes to fluorescently label and monitor polyclonal populations of thymocytes that are specific for moth cytochrome c (MCC)/I-Ek. In TCR β mice tetramer-positive thymocytes are detectable even in the most immature TCR-expressing cells. In the presence of MCC peptide, thymocytes that bind strongly to MCC/I-Ek tetramers are deleted earlier in development and more extensively than cells that bind weakly. This negative selection of the MCC/I-Ek-specific cells occurs continuously throughout development and before any evidence of positive selection. Thus, positive and negative selections are independent processes that need not occur sequentially.</jats:p>","journal":"The Journal of Immunology","year":1999,"id":646564,"datarank":0.635115975689589,"base_score":4.23410650459726,"endowment":4.23410650459726,"self_citation_contribution":0.635115975689589,"citation_network_contribution":0.0,"self_endowment_contribution":0.635115975689589,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":68,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1684175,"name":"Brian P Trenchak","orcid":null,"position":1,"is_corresponding":false},{"id":1684176,"name":"John D Altman","orcid":null,"position":2,"is_corresponding":false},{"id":1684177,"name":"Mark M Davis","orcid":null,"position":3,"is_corresponding":false},{"id":1684174,"name":"Kristin K Baldwin","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Negative Selection of T Cells Occurs Throughout Thymic Development","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Thymic positive and negative selections govern the development of a self-MHC-reactive, yet self-tolerant, T cell repertoire. Whether these processes occur independently or sequentially remains controversial. To investigate these issues, we have employed tetrameric peptide-MHC complexes to fluorescently label and monitor polyclonal populations of thymocytes that are specific for moth cytochrome c (MCC)/I-Ek. In TCR β mice tetramer-positive thymocytes are detectable even in the most immature TCR-expressing cells. In the presence of MCC peptide, thymocytes that bind strongly to MCC/I-Ek tetramers are deleted earlier in development and more extensively than cells that bind weakly. This negative selection of the MCC/I-Ek-specific cells occurs continuously throughout development and before any evidence of positive selection. Thus, positive and negative selections are independent processes that need not occur sequentially.</jats:p>","is_dataset_classified":null,"base_score":4.23410650459726,"endowment":4.23410650459726,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"10395659","pmcid":null,"openalex_id":"https://openalex.org/W2136552649","authors":[],"funders":[{"funder_name":"NIAID NIH HHS","grant_id":"AI22511","title":null}],"total_grants":1,"fwci":2.188,"citation_percentile":0.88364196,"influential_citations":0,"citation_trend":[{"year":2013,"count":2},{"year":2014,"count":1},{"year":2015,"count":3},{"year":2016,"count":1},{"year":2017,"count":2},{"year":2018,"count":1},{"year":2020,"count":1},{"year":2021,"count":1},{"year":2022,"count":2}],"oa_status":"closed","license":"https://academic.oup.com/pages/standard-publication-reuse-rights","oa_locations":[{"url":"https://academic.oup.com/jimmunol/article-pdf/163/2/689/62147511/im149900689p.pdf","host_type":"publisher"},{"url":"https://doi.org/10.4049/jimmunol.163.2.689","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/10395659","host_type":"repository"}],"fields_of_study":["T-cell and B-cell Immunology","Immune Cell Function and Interaction","Immunotherapy and Immune Responses"],"mesh_terms":["Amino Acid Sequence","Animals","Histocompatibility Antigens Class II","Cell Differentiation","Cytochrome c Group","Mice, Inbred C57BL","Mice, Transgenic","Molecular Sequence Data","Moths","Protein Binding","Receptors, Antigen, T-Cell","T-Lymphocytes","Thymus Gland","Time Factors","Clonal Deletion","Epitopes, T-Lymphocyte","Mice"],"keywords":["Negative selection","T-cell receptor","Positive selection","Biology","Major histocompatibility complex","Polyclonal antibodies","Clonal deletion","Tetramer","Cell biology","Thymocyte","Self Tolerance","T cell","Central tolerance","Immunology","Molecular biology","Antigen","Genetics","Gene","Biochemistry","Immune system"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-09T13:50:09.649945Z","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":[]}