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http://purl.uniprot.org/citations/25808313http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/25808313http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/25808313http://www.w3.org/2000/01/rdf-schema#comment"

Background

Presentation 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.

Results

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.

Conclusions

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."xsd:string
http://purl.uniprot.org/citations/25808313http://purl.org/dc/terms/identifier"doi:10.1186/s12977-015-0149-5"xsd:string
http://purl.uniprot.org/citations/25808313http://purl.org/dc/terms/identifier"doi:10.1186/s12977-015-0149-5"xsd:string
http://purl.uniprot.org/citations/25808313http://purl.uniprot.org/core/author"Carlson J."xsd:string
http://purl.uniprot.org/citations/25808313http://purl.uniprot.org/core/author"Carlson J."xsd:string
http://purl.uniprot.org/citations/25808313http://purl.uniprot.org/core/author"Rizkallah P.J."xsd:string
http://purl.uniprot.org/citations/25808313http://purl.uniprot.org/core/author"Rizkallah P.J."xsd:string
http://purl.uniprot.org/citations/25808313http://purl.uniprot.org/core/author"Buus S."xsd:string
http://purl.uniprot.org/citations/25808313http://purl.uniprot.org/core/author"Buus S."xsd:string
http://purl.uniprot.org/citations/25808313http://purl.uniprot.org/core/author"Sewell A.K."xsd:string
http://purl.uniprot.org/citations/25808313http://purl.uniprot.org/core/author"Sewell A.K."xsd:string
http://purl.uniprot.org/citations/25808313http://purl.uniprot.org/core/author"Cole D.K."xsd:string
http://purl.uniprot.org/citations/25808313http://purl.uniprot.org/core/author"Cole D.K."xsd:string
http://purl.uniprot.org/citations/25808313http://purl.uniprot.org/core/author"Beck K."xsd:string
http://purl.uniprot.org/citations/25808313http://purl.uniprot.org/core/author"Beck K."xsd:string
http://purl.uniprot.org/citations/25808313http://purl.uniprot.org/core/author"Schauenburg A.J."xsd:string
http://purl.uniprot.org/citations/25808313http://purl.uniprot.org/core/author"Schauenburg A.J."xsd:string
http://purl.uniprot.org/citations/25808313http://purl.uniprot.org/core/author"Fuller A."xsd:string
http://purl.uniprot.org/citations/25808313http://purl.uniprot.org/core/author"Fuller A."xsd:string
http://purl.uniprot.org/citations/25808313http://purl.uniprot.org/core/author"Goulder P."xsd:string
http://purl.uniprot.org/citations/25808313http://purl.uniprot.org/core/author"Goulder P."xsd:string
http://purl.uniprot.org/citations/25808313http://purl.uniprot.org/core/author"Kloverpris H.N."xsd:string
http://purl.uniprot.org/citations/25808313http://purl.uniprot.org/core/author"Kloverpris H.N."xsd:string
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