{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T00:02:48Z","timestamp":1768694568619,"version":"3.49.0"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T00:00:00Z","timestamp":1590969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>During normal T cell development in the thymus, \u03b1\u03b2 TCRs signal immature thymocytes to differentiate into mature T cells by binding to peptide\u2013MHC 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 V\u03b1\u03b2-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 V\u03b1\/V\u03b2 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.<\/jats:p>","DOI":"10.4049\/jimmunol.1901084","type":"journal-article","created":{"date-parts":[[2020,4,22]],"date-time":"2020-04-22T19:35:18Z","timestamp":1587584118000},"page":"3351-3359","source":"Crossref","is-referenced-by-count":9,"title":["Structure of MHC-Independent TCRs and Their Recognition of Native Antigen CD155"],"prefix":"10.1093","volume":"204","author":[{"given":"Jinghua","family":"Lu","sequence":"first","affiliation":[{"name":"Structural Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases , Rockville, MD 20852"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fran\u00e7ois","family":"Van Laethem","sequence":"additional","affiliation":[{"name":"Experimental Immunology Branch, National Cancer Institute , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0851-421X","authenticated-orcid":false,"given":"Ingrid","family":"Saba","sequence":"additional","affiliation":[{"name":"Experimental Immunology Branch, National Cancer Institute , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8520-1439","authenticated-orcid":false,"given":"Jonathan","family":"Chu","sequence":"additional","affiliation":[{"name":"Structural Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases , Rockville, MD 20852"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anastasia N","family":"Tikhonova","sequence":"additional","affiliation":[{"name":"Experimental Immunology Branch, National Cancer Institute , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1667-7169","authenticated-orcid":false,"given":"Abhisek","family":"Bhattacharya","sequence":"additional","affiliation":[{"name":"Experimental Immunology Branch, National Cancer Institute , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6780-5108","authenticated-orcid":false,"given":"Alfred","family":"Singer","sequence":"additional","affiliation":[{"name":"Experimental Immunology Branch, National Cancer Institute , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter D","family":"Sun","sequence":"additional","affiliation":[{"name":"Structural Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases , Rockville, MD 20852"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,6,15]]},"reference":[{"key":"2025030417512223700_r1","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1038\/s41467-019-08906-7","article-title":"Molecular constraints on CDR3 for thymic selection of MHC-restricted TCRs from a random pre-selection repertoire","volume":"10","author":"Lu","year":"2019","journal-title":"Nat. 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