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within T cell epitopes represent a common mechanism of viral escape from the host protective immune response. The diverse T cell repertoire and the extensive human leukocyte antigen (HLA) polymorphism across populations is the evolutionary response to viral mutation. However, the molecular basis underpinning the interplay between HLA polymorphism, the T cell repertoire, and viral escape is unclear. Here we investigate the T cell response to a HLA-B*35:01- and HLA-B*35:08-restricted (407)HPVGEADYFEY(417) epitope from Epstein-Barr virus and naturally occurring variants at positions 4 and 5 thereof. Each viral variant differently impacted on the epitope's flexibility and conformation when bound to HLA-B*35:08 or HLA-B*35:01. We provide a molecular basis for understanding how the single residue polymorphism that discriminates between HLA-B*35:01/08 profoundly impacts on T cell receptor recognition. Surprisingly, one viral variant (P5-Glu to P5-Asp) effectively changed restriction preference from HLA-B*35:01 to HLA-B*35:08. Collectively, our study portrays the interplay between the T cell response, viral escape, and HLA polymorphism, whereby HLA polymorphism enables altered presentation of epitopes from different strains of Epstein-Barr virus.","bibjson":{"author":[{"initials":"YC","lastname":"Liu","name":"Liu YC"},{"initials":"Z","lastname":"Chen","name":"Chen Z"},{"initials":"MA","lastname":"Neller","name":"Neller MA"},{"initials":"JJ","lastname":"Miles","name":"Miles JJ"},{"initials":"AW","lastname":"Purcell","name":"Purcell AW"},{"initials":"J","lastname":"McCluskey","name":"McCluskey J"},{"initials":"SR","lastname":"Burrows","name":"Burrows SR"},{"initials":"J","lastname":"Rossjohn","name":"Rossjohn J"},{"initials":"S","lastname":"Gras","name":"Gras S"}],"identifier":[{"id":"10.1074/jbc.M114.563502","type":"doi"},{"id":"24759101","type":"pubmed"}],"issue":["24"],"journal":{"iso_abbreviation":"J. Biol. Chem.","name":""},"pages":["16688-16698"],"title":"A Molecular Basis for the Interplay between T Cells, Viral Mutants, and Human Leukocyte Antigen Micropolymorphism.","type":"article","url":"https://www.sciencedirect.com/science/article/abs/pii/S002192582040643X","volume":["289"],"year":[2014]},"in_pmc":"N","in_pmce":"Y","open_access":"N"},"resolution":"2.50","same_as":{"pdbe":{"url":"https://www.ebi.ac.uk/pdbe/entry/pdb/4prh"},"rcsb":{"url":"https://www.rcsb.org/structure/4prh"},"stcrdab":{"url":"http://opig.stats.ox.ac.uk/webapps/stcrdab/StrViewer?pdb=4prh"}},"species":{"common_name":"Human","match_type":"histo:assign_species","scientific_name":"Homo sapiens","slug":"homo_sapiens"},"tcr":{"alpha":{"chains":["D"],"subgroup":"TRAV20"},"beta":{"chains":["E"],"subgroup":"TRBV9"},"mhc_type":"class_i","pdb_code":"4prh"},"title":"HLA-B*35:01 presenting \"HPVGDADYFEY\" to Alpha/Beta T cell receptor at 2.50Å resolution","unique_chain_count":5}}