{"doi":"10.1126/science.abe0918","title":"Pre–T cell receptors topologically sample self-ligands during thymocyte β-selection","abstract":"Self-discrimination, a critical but ill-defined molecular process programmed during thymocyte development, requires myriad pre-T cell receptors (preTCRs) and αβTCRs. Using x-ray crystallography, we show how a preTCR applies the concave β-sheet surface of its single variable domain (Vβ) to \"horizontally\" grab the protruding MHC α2-helix. By contrast, αβTCRs purpose all six complementarity-determining region (CDR) loops of their paired VαVβ module to recognize peptides bound to major histocompatibility complex molecules (pMHCs) in \"vertical\" head-to-head binding. The preTCR topological fit ensures that CDR3β reaches the peptide's featured C-terminal segment for pMHC sampling, establishing the subsequent αβTCR canonical docking mode. \"Horizontal\" docking precludes germline CDR1β- and CDR2β-MHC binding to broaden β-chain repertoire diversification before αβTCR-mediated selection refinement. Thus, one subunit successively attunes the recognition logic of related multicomponent receptors.","journal":"Science","year":2021,"id":163457,"datarank":0.5606504427425053,"base_score":3.7376696182833684,"endowment":3.7376696182833684,"self_citation_contribution":0.5606504427425053,"citation_network_contribution":0.0,"self_endowment_contribution":0.5606504427425053,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":41,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9459,"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":683239,"name":"Réka Mizsei","orcid":"0000-0003-4519-4307","position":1,"is_corresponding":false},{"id":502647,"name":"Kemin Tan","orcid":"0000-0002-4003-7903","position":2,"is_corresponding":false},{"id":683240,"name":"Robert J. Mallis","orcid":"0000-0002-2087-9468","position":3,"is_corresponding":false},{"id":253966,"name":"Jonathan S. Duke‐Cohan","orcid":"0000-0002-9478-9609","position":4,"is_corresponding":false},{"id":622803,"name":"Aoi Akitsu","orcid":"0000-0001-7672-9664","position":5,"is_corresponding":false},{"id":683241,"name":"Paul W. Tetteh","orcid":"0000-0003-4381-498X","position":6,"is_corresponding":false},{"id":407357,"name":"Abhinav Dubey","orcid":"0000-0002-2392-8050","position":7,"is_corresponding":false},{"id":444225,"name":"Wonmuk Hwang","orcid":"0000-0001-7514-3186","position":8,"is_corresponding":false},{"id":137366,"name":"Gerhard Wagner","orcid":"0000-0002-2063-4401","position":9,"is_corresponding":false},{"id":683242,"name":"Matthew J. Lang","orcid":"0000-0002-8198-144X","position":10,"is_corresponding":false},{"id":218700,"name":"Haribabu Arthanari","orcid":"0000-0002-7281-1289","position":11,"is_corresponding":false},{"id":680279,"name":"Jia‐Huai Wang","orcid":"0000-0003-3478-829X","position":12,"is_corresponding":false},{"id":622807,"name":"Ellis L. Reinherz","orcid":"0000-0003-1048-5526","position":13,"is_corresponding":false},{"id":683238,"name":"Xiaolong Li","orcid":"0000-0001-6549-4089","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:45:22.477398Z","pmid":"33335016","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":[]}