{"doi":"10.7554/elife.65435","title":"T cell self-reactivity during thymic development dictates the timing of positive selection","abstract":"Functional tuning of T cells based on their degree of self-reactivity is established during positive selection in the thymus, although how positive selection differs for thymocytes with relatively low versus high self-reactivity is unclear. In addition, preselection thymocytes are highly sensitive to low-affinity ligands, but the mechanism underlying their enhanced T cell receptor (TCR) sensitivity is not fully understood. Here we show that murine thymocytes with low self-reactivity experience briefer TCR signals and complete positive selection more slowly than those with high self-reactivity. Additionally, we provide evidence that cells with low self-reactivity retain a preselection gene expression signature as they mature, including genes previously implicated in modulating TCR sensitivity and a novel group of ion channel genes. Our results imply that thymocytes with low self-reactivity downregulate TCR sensitivity more slowly during positive selection, and associate membrane ion channel expression with thymocyte self-reactivity and progress through positive selection.","journal":"eLife","year":2021,"id":171593,"datarank":0.8622713153642785,"base_score":3.295836866004329,"endowment":3.295836866004329,"self_citation_contribution":0.4943755299006494,"citation_network_contribution":0.3678957854636291,"self_endowment_contribution":0.4943755299006494,"citer_contribution":0.3678957854636291,"corpus_percentile":null,"corpus_rank":null,"citation_count":26,"citer_count":20,"citers_with_citation_signal":13,"citers_with_endowment":13,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE164896","GSE62142","GSE151395","GSE15907"]},"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":556292,"name":"Zoë Steier","orcid":"0000-0003-1488-7995","position":1,"is_corresponding":false},{"id":706379,"name":"Laura L. McIntyre","orcid":"0000-0001-7820-4431","position":2,"is_corresponding":false},{"id":707036,"name":"Shraddha Pandey","orcid":null,"position":3,"is_corresponding":false},{"id":615916,"name":"James J. Kaminski","orcid":"0000-0002-5137-7516","position":4,"is_corresponding":false},{"id":272333,"name":"Ashley R. Hoover","orcid":"0000-0002-3555-1510","position":5,"is_corresponding":false},{"id":706380,"name":"Silvia Ariotti","orcid":"0000-0002-2151-3812","position":6,"is_corresponding":false},{"id":18056,"name":"Aaron Streets","orcid":"0000-0002-3909-8389","position":7,"is_corresponding":false},{"id":858,"name":"Nir Yosef","orcid":"0000-0001-9004-1225","position":8,"is_corresponding":false},{"id":372451,"name":"Ellen A. Robey","orcid":"0000-0002-3630-5266","position":9,"is_corresponding":false},{"id":372450,"name":"Lydia K. Lutes","orcid":"0000-0001-6133-6294","position":0,"is_corresponding":true}],"reference_count":90,"raw_metadata":null,"created_at":"2026-07-18T23:46:33.067299Z","pmid":"33884954","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":[]}