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of identical HIV-1 peptides by closely related Human Leukocyte Antigen class I (HLAI) molecules can select distinct patterns of escape mutation that have a significant impact on viral fitness and disease progression. The molecular mechanisms by which HLAI micropolymorphisms can induce differential HIV-1 escape patterns within identical peptide epitopes remain unknown.<h4>Results</h4>Here, we undertook genetic and structural analyses of two immunodominant HIV-1 peptides, Gag180-188 (TPQDLNTML, TL9-p24) and Nef71-79 (RPQVPLRPM, RM9-Nef) that are among the most highly targeted epitopes in the global HIV-1 epidemic. We show that single polymorphisms between different alleles of the HLA-B7 superfamily can induce a conformational switch in peptide conformation that is associated with differential HLAI-specific escape mutation and immune control. A dominant R71K mutation in the Nef71-79 occurred in those with HLA-B*07:02 but not B*42:01/02 or B*81:01. No structural difference in the HLA-epitope complexes was detected to explain this observation.<h4>Conclusions</h4>These data suggest that identical peptides presented through very similar HLAI landscapes are recognized as distinct epitopes and provide a novel structural mechanism for previously observed differential HIV-1 escape and disease progression.","bibjson":{"author":[{"initials":"HN","lastname":"Kl\u00f8verpris","name":"Kl\u00f8verpris HN"},{"initials":"DK","lastname":"Cole","name":"Cole DK"},{"initials":"A","lastname":"Fuller","name":"Fuller A"},{"initials":"J","lastname":"Carlson","name":"Carlson J"},{"initials":"K","lastname":"Beck","name":"Beck K"},{"initials":"AJ","lastname":"Schauenburg","name":"Schauenburg AJ"},{"initials":"PJ","lastname":"Rizkallah","name":"Rizkallah PJ"},{"initials":"S","lastname":"Buus","name":"Buus S"},{"initials":"AK","lastname":"Sewell","name":"Sewell AK"},{"initials":"P","lastname":"Goulder","name":"Goulder P"}],"identifier":[{"id":"10.1186/s12977-015-0149-5","type":"doi"},{"id":"25808313","type":"pubmed"}],"issue":["1"],"journal":{"iso_abbreviation":"Retrovirology","name":""},"pages":["20"],"title":"A molecular switch in immunodominant HIV-1-specific CD8 T-cell epitopes shapes differential HLA-restricted escape.","type":"article","url":"https://retrovirology.biomedcentral.com/articles/10.1186/s12977-015-0149-5","volume":["12"],"year":[2015]},"in_pmc":"N","in_pmce":"Y","open_access":"Y"},"resolution":"1.18","same_as":{"pdbe":{"url":"https://www.ebi.ac.uk/pdbe/entry/pdb/4u1m"},"rcsb":{"url":"https://www.rcsb.org/structure/4u1m"}},"species":{"common_name":"Human","match_type":"histo:assign_species","scientific_name":"Homo sapiens","slug":"homo_sapiens"},"tcr":null,"title":"HLA-B*42:01 binding \"RPQVPLRPM\" at 1.18&#8491; resolution","unique_chain_count":3}}