{"doi":"10.4049/jimmunol.1901084","title":"Structure of MHC-Independent TCRs and Their Recognition of Native Antigen CD155","abstract":"During normal T cell development in the thymus, αβ TCRs signal immature thymocytes to differentiate into mature T cells by binding to peptide-MHC ligands together with CD4/CD8 coreceptors. Conversely, in MHC and CD4/CD8 coreceptor-deficient mice, the thymus generates mature T cells expressing MHC-independent TCRs that recognize native conformational epitopes rather than linear antigenic-peptides presented by MHC. To date, no structural information of MHC-independent TCRs is available, and their structural recognition of non-MHC ligand remains unknown. To our knowledge in this study, we determined the first structures of two murine MHC-independent TCRs (A11 and B12A) that bind with high nanomolar affinities to mouse adhesion receptor CD155. Solution binding demonstrated the Vαβ-domain is responsible for MHC-independent B12A recognition of its ligand. Analysis of A11 and B12A sequences against various MHC-restricted and -independent TCR sequence repertoires showed that individual V-genes of A11 and B12A did not exhibit preference against MHC-restriction. Likewise, CDR3 alone did not discriminate against MHC binding, suggesting VDJ recombination together with Vα/Vβ pairing determine their MHC-independent specificity for CD155. The structures of A11 and B12A TCR are nearly identical to those of MHC-restricted TCR, including the conformations of CDR1 and 2. Mutational analysis, together with negative-staining electron microscopy images, showed that the CDR regions of A11 and B12A recognized epitopes on D1 domain of CD155, a region also involved in CD155 binding to poliovirus and Tactile in human. Taken together, MHC-independent TCRs adopt canonical TCR structures to recognize native Ags, highlighting the importance of thymic selection in determining TCR ligand specificity.","journal":"The Journal of Immunology","year":2020,"id":88965,"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":0.9492,"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":450766,"name":"François Van Laethem","orcid":"0000-0002-0417-0715","position":1,"is_corresponding":false},{"id":450767,"name":"Ingrid Saba","orcid":"0000-0003-0851-421X","position":2,"is_corresponding":false},{"id":420500,"name":"Jonathan Chu","orcid":"0000-0002-8520-1439","position":3,"is_corresponding":false},{"id":247442,"name":"Anastasia N. Tikhonova","orcid":"0000-0001-6712-1606","position":4,"is_corresponding":false},{"id":450768,"name":"Abhisek Bhattacharya","orcid":"0000-0002-1667-7169","position":5,"is_corresponding":false},{"id":450769,"name":"Alfred Singer","orcid":"0000-0002-6780-5108","position":6,"is_corresponding":false},{"id":271698,"name":"Peter D. Sun","orcid":"0000-0003-0475-1891","position":7,"is_corresponding":false},{"id":271697,"name":"Jinghua Lu","orcid":"0000-0001-7169-1687","position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-18T22:01:50.225871Z","pmid":"32321756","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":[]}