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HLA class I alleles can bind epitopes up to 14 amino acids in length, little is known about the immunogenicity or the responding T-cell repertoire against such determinants. Here, we describe an HLA-B*3508-restricted cytotoxic T lymphocyte response to a 13-mer viral epitope (LPEPLPQGQLTAY). The rigid, centrally bulged epitope generated a biased T-cell response. Only the N-terminal face of the peptide bulge was critical for recognition by the dominant clonotype SB27. The SB27 public T-cell receptor (TcR) associated slowly onto the complex between the bulged peptide and the major histocompatibility complex, suggesting significant remodeling upon engagement. The broad antigen-binding cleft of HLA-B*3508 represents a critical feature for engagement of the public TcR, as the narrower binding cleft of HLA-B*3501(LPEPLPQGQLTAY), which differs from HLA-B*3508 by a single amino acid polymorphism (Arg156 --> Leu), interacted poorly with the dominant TcR. Biased TcR usage in this cytotoxic T lymphocyte response appears to reflect a dominant role of the prominent peptide x major histocompatibility complex class I surface.","bibjson":{"author":[{"initials":"FE","lastname":"Tynan","name":"Tynan FE"},{"initials":"NA","lastname":"Borg","name":"Borg NA"},{"initials":"JJ","lastname":"Miles","name":"Miles JJ"},{"initials":"T","lastname":"Beddoe","name":"Beddoe T"},{"initials":"D","lastname":"El-Hassen","name":"El-Hassen D"},{"initials":"SL","lastname":"Silins","name":"Silins SL"},{"initials":"WJ","lastname":"van Zuylen","name":"van Zuylen WJ"},{"initials":"AW","lastname":"Purcell","name":"Purcell AW"},{"initials":"L","lastname":"Kjer-Nielsen","name":"Kjer-Nielsen L"},{"initials":"J","lastname":"McCluskey","name":"McCluskey J"},{"initials":"SR","lastname":"Burrows","name":"Burrows SR"},{"initials":"J","lastname":"Rossjohn","name":"Rossjohn J"}],"identifier":[{"id":"10.1074/jbc.m503060200","type":"doi"},{"id":"15849183","type":"pubmed"}],"issue":["25"],"journal":{"iso_abbreviation":"J. Biol. Chem.","name":""},"pages":["23900-9"],"title":"High resolution structures of highly bulged viral epitopes bound to major histocompatibility complex class I. Implications for T-cell receptor engagement and T-cell immunodominance.","type":"article","url":"https://www.sciencedirect.com/science/article/abs/pii/S0021925820674476","volume":["280"],"year":[2005]},"in_pmc":"N","in_pmce":"N","open_access":"N"},"resolution":"1.50","same_as":{"pdbe":{"url":"https://www.ebi.ac.uk/pdbe/entry/pdb/1zhl"},"rcsb":{"url":"https://www.rcsb.org/structure/1zhl"}},"species":{"common_name":"Human","match_type":"histo:assign_species","scientific_name":"Homo sapiens","slug":"homo_sapiens"},"tcr":null,"title":"HLA-B*35:08 binding \"LPEPLPQGQLTAY\" at 1.50Å resolution","unique_chain_count":3}}