AIDS-protective HLA-B*27/B*57 and chimpanzee MHC class I molecules target analogous conserved areas of HIV-1/SIVcpz

Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15175-80. doi: 10.1073/pnas.1009136107. Epub 2010 Aug 9.

Abstract

In the absence of treatment, most HIV-1-infected humans develop AIDS. However, a minority are long-term nonprogressors, and resistance is associated with the presence of particular HLA-B*27/B*57 molecules. In contrast, most HIV-1-infected chimpanzees do not contract AIDS. In comparison with humans, chimpanzees experienced an ancient selective sweep affecting the MHC class I repertoire. We have determined the peptide-binding properties of frequent chimpanzee MHC class I molecules, and show that, like HLA-B*27/B*57, they target similar conserved areas of HIV-1/SIV(cpz). In addition, many animals appear to possess multiple molecules targeting various conserved areas of the HIV-1/SIV(cpz) Gag protein, a quantitative aspect of the immune response that may further minimize the chance of viral escape. The functional characteristics of the contemporary chimpanzee MHC repertoire suggest that the selective sweep was caused by a lentiviral pandemic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome / genetics
  • Acquired Immunodeficiency Syndrome / immunology
  • Acquired Immunodeficiency Syndrome / prevention & control*
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Conserved Sequence
  • Gene Products, gag / genetics
  • Gene Products, gag / metabolism
  • Genes, MHC Class I
  • HIV Long-Term Survivors
  • HIV-1 / genetics*
  • HIV-1 / immunology*
  • HLA-B Antigens / genetics*
  • HLA-B27 Antigen / genetics*
  • Histocompatibility Antigens Class I / genetics*
  • Humans
  • Molecular Sequence Data
  • Pan troglodytes / genetics*
  • Pan troglodytes / immunology*
  • Protein Binding
  • Simian Immunodeficiency Virus / genetics*
  • Simian Immunodeficiency Virus / immunology*
  • Species Specificity
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • Gene Products, gag
  • HLA-B Antigens
  • HLA-B27 Antigen
  • HLA-B57 antigen
  • Histocompatibility Antigens Class I