{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Mazza C"],"funding":["Medical Research Council"],"pagination":["1972-83"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC1847653"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["26(7)"],"pubmed_abstract":["Binding degeneracy is thought to constitute a fundamental property of the T-cell antigen receptor (TCR), yet its structural basis is poorly understood. We determined the crystal structure of a complex involving the BM3.3 TCR and a peptide (pBM8) bound to the H-2K(bm8) major histocompatibility complex (MHC) molecule, and compared it with the structures of the BM3.3 TCR bound to H-2K(b) molecules loaded with two peptides that had a minimal level of primary sequence identity with pBM8. Our findings provide a refined structural view of the basis of BM3.3 TCR cross-reactivity and a structural explanation for the long-standing paradox that a TCR antigen-binding site can be both specific and degenerate. We also measured the thermodynamic features and biological penalties that incurred during cross-recognition. Our data illustrate the difficulty for a given TCR in adapting to distinct peptide-MHC surfaces while still maintaining affinities that result in functional in vivo responses. Therefore, when induction of protective effector T cells is used as the ultimate criteria for adaptive immunity, TCRs are probably much less degenerate than initially assumed."],"journal":["The EMBO journal"],"pubmed_title":["How much can a T-cell antigen receptor adapt to structurally distinct antigenic peptides?"],"pmcid":["PMC1847653"],"funding_grant_id":["G9722488"],"pubmed_authors":["Auphan-Anezin N","Mazza C","van der Merwe PA","Roussel A","Gregoire C","Schmitt-Verhulst AM","Guimezanes A","Kellenberger C","Kearney A","Malissen B"],"additional_accession":[]},"is_claimable":false,"name":"How much can a T-cell antigen receptor adapt to structurally distinct antigenic peptides?","description":"Binding degeneracy is thought to constitute a fundamental property of the T-cell antigen receptor (TCR), yet its structural basis is poorly understood. We determined the crystal structure of a complex involving the BM3.3 TCR and a peptide (pBM8) bound to the H-2K(bm8) major histocompatibility complex (MHC) molecule, and compared it with the structures of the BM3.3 TCR bound to H-2K(b) molecules loaded with two peptides that had a minimal level of primary sequence identity with pBM8. Our findings provide a refined structural view of the basis of BM3.3 TCR cross-reactivity and a structural explanation for the long-standing paradox that a TCR antigen-binding site can be both specific and degenerate. We also measured the thermodynamic features and biological penalties that incurred during cross-recognition. Our data illustrate the difficulty for a given TCR in adapting to distinct peptide-MHC surfaces while still maintaining affinities that result in functional in vivo responses. Therefore, when induction of protective effector T cells is used as the ultimate criteria for adaptive immunity, TCRs are probably much less degenerate than initially assumed.","dates":{"release":"2007-01-01T00:00:00Z","publication":"2007 Apr","modification":"2021-02-20T06:50:01Z","creation":"2019-03-27T02:03:42Z"},"accession":"S-EPMC1847653","cross_references":{"pubmed":["17363906"],"doi":["10.1038/sj.emboj.7601605"]}}