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capacity of the immune system to adapt to rapidly evolving viruses is a primary feature of effective immunity, yet its molecular basis is unclear. Here, we investigated protective HIV-1-specific CD8+ T cell responses directed against the immunodominant p24 Gag-derived epitope KK10 (KRWIILGLNK263-272) presented by human leukocyte antigen (HLA)-B\u22172705. We found that cross-reactive CD8+ T cell clonotypes were mobilized to counter the rapid emergence of HIV-1 variants that can directly affect T cell receptor (TCR) recognition. These newly recruited clonotypes expressed TCRs that engaged wild-type and mutant KK10 antigens with similar affinities and almost identical docking modes, thereby accounting for their antiviral efficacy in HLA-B\u22172705+ individuals. A protective CD8+ T cell repertoire therefore encompasses the capacity to control TCR-accessible mutations, ultimately driving the development of more complex viral escape variants that disrupt antigen presentation.","bibjson":{"author":[{"initials":"K","lastname":"Ladell","name":"Ladell K"},{"initials":"M","lastname":"Hashimoto","name":"Hashimoto M"},{"initials":"MC","lastname":"Iglesias","name":"Iglesias MC"},{"initials":"PG","lastname":"Wilmann","name":"Wilmann PG"},{"initials":"JE","lastname":"McLaren","name":"McLaren JE"},{"initials":"S","lastname":"Gras","name":"Gras S"},{"initials":"T","lastname":"Chikata","name":"Chikata T"},{"initials":"N","lastname":"Kuse","name":"Kuse N"},{"initials":"S","lastname":"Fastenackels","name":"Fastenackels S"},{"initials":"E","lastname":"Gostick","name":"Gostick E"},{"initials":"JS","lastname":"Bridgeman","name":"Bridgeman JS"},{"initials":"V","lastname":"Venturi","name":"Venturi V"},{"initials":"ZA","lastname":"Arkoub","name":"Arkoub ZA"},{"initials":"H","lastname":"Agut","name":"Agut H"},{"initials":"DJ","lastname":"van Bockel","name":"van Bockel DJ"},{"initials":"JR","lastname":"Almeida","name":"Almeida JR"},{"initials":"DC","lastname":"Douek","name":"Douek DC"},{"initials":"L","lastname":"Meyer","name":"Meyer L"},{"initials":"A","lastname":"Venet","name":"Venet A"},{"initials":"M","lastname":"Takiguchi","name":"Takiguchi M"},{"initials":"J","lastname":"Rossjohn","name":"Rossjohn J"},{"initials":"DA","lastname":"Price","name":"Price DA"},{"initials":"V","lastname":"Appay","name":"Appay V"}],"identifier":[{"id":"10.1016/j.immuni.2012.11.021","type":"doi"},{"id":"23521884","type":"pubmed"}],"issue":["3"],"journal":{"iso_abbreviation":"Immunity","name":""},"pages":["425-36"],"title":"A Molecular Basis for the Control of Preimmune Escape Variants by HIV-Specific CD8(+) T Cells.","type":"article","url":"https://www.sciencedirect.com/science/article/abs/pii/S1074761313001064","volume":["38"],"year":[2013]},"in_pmc":"N","in_pmce":"N","open_access":"N"},"resolution":"2.40","same_as":{"pdbe":{"url":"https://www.ebi.ac.uk/pdbe/entry/pdb/4g8g"},"rcsb":{"url":"https://www.rcsb.org/structure/4g8g"},"stcrdab":{"url":"http://opig.stats.ox.ac.uk/webapps/stcrdab/StrViewer?pdb=4g8g"}},"species":{"common_name":"Human","match_type":"histo:assign_species","scientific_name":"Homo sapiens","slug":"homo_sapiens"},"tcr":{"alpha":{"chains":["D"],"subgroup":"TRAV14"},"beta":{"chains":["E"],"subgroup":"TRBV6"},"mhc_type":"class_i","pdb_code":"4g8g"},"title":"HLA-B*27:05 presenting \"KRWIILGLNK\" to Alpha/Beta T cell receptor at 2.40Å resolution","unique_chain_count":5}}