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

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Kløverpris HN, Cole DK, Fuller A, Carlson J, Beck K, Schauenburg AJ, Rizkallah PJ, Buus S, Sewell AK, Goulder P
OpenAccess logo Retrovirology 12 20 (2015)
Related entries: 4u1h, 4u1i, 4u1k, 4u1l, 4u1m, 4u1n, 4u1s

Cited: 29 times
EuropePMC logo PMID: 25808313

Abstract

Background
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.

Conclusion

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.

Articles - 4u1j mentioned but not cited (2)

  1. A molecular switch in immunodominant HIV-1-specific CD8 T-cell epitopes shapes differential HLA-restricted escape. Kløverpris HN, Cole DK, Fuller A, Carlson J, Beck K, Schauenburg AJ, Rizkallah PJ, Buus S, Sewell AK, Goulder P. Retrovirology 12 20 (2015)
  2. Structural basis of the TCR-pHLA complex provides insights into the unconventional recognition of CDR3β in TCR cross-reactivity and alloreactivity. San D, Lei J, Liu Y, Jing B, Ye X, Wei P, Paek C, Yang Y, Zhou J, Chen P, Wang H, Chen Y, Yin L. Cell Insight 2 100076 (2023)


Reviews citing this publication (4)

  1. The pockets guide to HLA class I molecules. Nguyen AT, Szeto C, Gras S. Biochem Soc Trans 49 2319-2331 (2021)
  2. Role of HLA Adaptation in HIV Evolution. Kløverpris HN, Leslie A, Goulder P. Front Immunol 6 665 (2015)
  3. T Cell Epitope Discovery in the Context of Distinct and Unique Indigenous HLA Profiles. Hensen L, Illing PT, Rowntree LC, Davies J, Miller A, Tong SYC, Habel JR, van de Sandt CE, Flanagan KL, Purcell AW, Kedzierska K, Clemens EB. Front Immunol 13 812393 (2022)
  4. Unconventional modes of peptide-HLA-I presentation change the rules of TCR engagement. Hopkins JR, MacLachlan BJ, Harper S, Sewell AK, Cole DK. Discov Immunol 1 kyac001 (2022)

Articles citing this publication (23)



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