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T-cell responses to persistent viral infections are characterized by the accumulation of an oligoclonal T-cell repertoire and a reduction in the naive T-cell pool. However, the precise mechanism for this phenomenon remains elusive. Here we show that human cytomegalovirus (HCMV)-specific CD8(+) T cells recognizing distinct epitopes from the pp65 protein and restricted through an identical HLA class I allele (HLA B*3508) exhibited either a highly conserved public T-cell repertoire or a private, diverse T-cell response, which was uniquely altered in each donor following in vitro antigen exposure. Selection of a public T-cell receptor (TCR) was coincident with an atypical major histocompatibility complex (MHC)-peptide structure, in that the epitope adopted a helical conformation that bulged from the peptide-binding groove, while a diverse TCR profile was observed in response to the epitope that formed a flatter, more \"featureless\" landscape. Clonotypes with biased TCR usage demonstrated more efficient recognition of virus-infected cells, a greater CD8 dependency, and were more terminally differentiated in their phenotype when compared with the T cells expressing diverse TCR. These findings provide new insights into our understanding on how the biology of antigen presentation in addition to the structural features of the pMHC-I might shape the T-cell repertoire and its phenotype.","bibjson":{"author":[{"initials":"KK","lastname":"Wynn","name":"Wynn KK"},{"initials":"Z","lastname":"Fulton","name":"Fulton Z"},{"initials":"L","lastname":"Cooper","name":"Cooper L"},{"initials":"SL","lastname":"Silins","name":"Silins SL"},{"initials":"S","lastname":"Gras","name":"Gras S"},{"initials":"JK","lastname":"Archbold","name":"Archbold JK"},{"initials":"FE","lastname":"Tynan","name":"Tynan FE"},{"initials":"JJ","lastname":"Miles","name":"Miles JJ"},{"initials":"J","lastname":"McCluskey","name":"McCluskey J"},{"initials":"SR","lastname":"Burrows","name":"Burrows SR"},{"initials":"J","lastname":"Rossjohn","name":"Rossjohn J"},{"initials":"R","lastname":"Khanna","name":"Khanna R"}],"identifier":[{"id":"10.1182/blood-2007-11-122622","type":"doi"},{"id":"18270323","type":"pubmed"}],"issue":["8"],"journal":{"iso_abbreviation":"Blood","name":""},"pages":["4283-92"],"title":"Impact of clonal competition for peptide-MHC complexes on the CD8+ T-cell repertoire selection in a persistent viral infection.","type":"article","url":"https://ashpublications.org/blood/article/111/8/4283/24620/Impact-of-clonal-competition-for-peptideMHC","volume":["111"],"year":[2008]},"in_pmc":"N","in_pmce":"N","open_access":"N"},"resolution":"1.75","same_as":{"pdbe":{"url":"https://www.ebi.ac.uk/pdbe/entry/pdb/3bw9"},"rcsb":{"url":"https://www.rcsb.org/structure/3bw9"}},"species":{"common_name":"Human","match_type":"histo:assign_species","scientific_name":"Homo sapiens","slug":"homo_sapiens"},"tcr":null,"title":"HLA-B*35:08 binding \"CPSQEPMSIYVY\" at 1.75Å resolution","unique_chain_count":3}}