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Instruments / Technical Area	Publication Details	Published	Actions
I04-1-Macromolecular Crystallography (fixed wavelength)	A molecular switch in immunodominant HIV-1-specific CD8 T-cell epitopes shapes differential HLA-restricted escape Henrik N Kløverpris , David K. Cole , Anna Fuller , Jonathan Carlson , Konrad Beck , Andrea J. Schauenburg , Pierre Rizkallah , Søren Buus , Andrew K. Sewell , Philip Goulder Retrovirology 12 DOI: 10.1186/s12977-015-0149-5 PMID: 25808313 Diamond Proposal Number(s): [8096] Open Access Show Abstract ▼ Abstract: 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-B07:02 but not B42:01/02 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.	Feb 2015

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I04-1-Macromolecular Crystallography (fixed wavelength)

A molecular switch in immunodominant HIV-1-specific CD8 T-cell epitopes shapes differential HLA-restricted escape

Henrik N Kløverpris , David K. Cole , Anna Fuller , Jonathan Carlson , Konrad Beck , Andrea J. Schauenburg , Pierre Rizkallah , Søren Buus , Andrew K. Sewell , Philip Goulder

Retrovirology 12

DOI: 10.1186/s12977-015-0149-5

PMID: 25808313

Diamond Proposal Number(s): [8096]