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T cells must recognize self-antigens in the thymus during maturation and then discriminate between foreign pathogens in the periphery. A molecular basis for this cross-reactivity is elucidated by the crystal structure of the alloreactive 2C TCR bound to self peptide-major histocompatibility complex (pMHC) antigen H-2Kb-dEV8 refined against anisotropic 3.0 angstrom resolution x-ray data. The interface between peptide and TCR exhibits extremely poor shape complementarity, and the TCR beta chain complementarity-determining region 3 (CDR3) has minimal interaction with the dEV8 peptide. Large conformational changes in three of the TCR CDR loops are induced upon binding, providing a mechanism of structural plasticity to accommodate a variety of different peptide antigens. Extensive TCR interaction with the pMHC alpha helices suggests a generalized orientation that is mediated by the Valpha domain of the TCR and rationalizes how TCRs can effectively \"scan\" different peptides bound within a large, low-affinity MHC structural framework for those that provide the slight additional kinetic stabilization required for signaling.","bibjson":{"author":[{"initials":"KC","lastname":"Garcia","name":"Garcia KC"},{"initials":"M","lastname":"Degano","name":"Degano M"},{"initials":"LR","lastname":"Pease","name":"Pease LR"},{"initials":"M","lastname":"Huang","name":"Huang M"},{"initials":"PA","lastname":"Peterson","name":"Peterson PA"},{"initials":"L","lastname":"Teyton","name":"Teyton L"},{"initials":"IA","lastname":"Wilson","name":"Wilson IA"}],"identifier":[{"id":"10.1126/science.279.5354.1166","type":"doi"},{"id":"9469799","type":"pubmed"}],"issue":["5354"],"journal":{"iso_abbreviation":"Science","name":""},"pages":["1166-72"],"title":"Structural basis of plasticity in T cell receptor recognition of a self peptide-MHC antigen.","type":"article","url":"https://www.science.org/doi/10.1126/science.279.5354.1166","volume":["279"],"year":[1998]},"in_pmc":"N","in_pmce":"N","open_access":"N"},"resolution":"3.00","same_as":{"pdbe":{"url":"https://www.ebi.ac.uk/pdbe/entry/pdb/2ckb"},"rcsb":{"url":"https://www.rcsb.org/structure/2ckb"},"stcrdab":{"url":"http://opig.stats.ox.ac.uk/webapps/stcrdab/StrViewer?pdb=2ckb"}},"species":{"common_name":"Mouse","match_type":"histo:assign_species","scientific_name":"Mus musculus","slug":"mus_musculus"},"tcr":{"alpha":{"chains":["A"],"subgroup":"TRAV9"},"beta":{"chains":["B"],"subgroup":"TRBV13"},"mhc_type":"class_i","pdb_code":"2ckb"},"title":"H2-Kb presenting \"EQYKFYSV\" to Alpha/Beta T cell receptor at 3.00&#8491; resolution","unique_chain_count":5}}
