MHC heterozygote advantage in simian immunodeficiency virus-infected Mauritian cynomolgus macaques

Sci Transl Med. 2010 Mar 10;2(22):22ra18. doi: 10.1126/scitranslmed.3000524.


The importance of a broad CD8 T lymphocyte (CD8-TL) immune response to HIV is unknown. Ex vivo measurements of immunological activity directed at a limited number of defined epitopes provide an incomplete portrait of the actual immune response. We examined viral loads in simian immunodeficiency virus (SIV)-infected major histocompatibility complex (MHC)-homozygous and MHC-heterozygous Mauritian cynomolgus macaques. Chronic viremia in MHC-homozygous macaques was 80 times that in MHC-heterozygous macaques. Virus from MHC-homozygous macaques accumulated 11 to 14 variants, consistent with escape from CD8-TL responses after 1 year of SIV infection. The pattern of mutations detected in MHC-heterozygous macaques suggests that their epitope-specific CD8-TL responses are a composite of those present in their MHC-homozygous counterparts. These results provide the clearest example of MHC heterozygote advantage among individuals infected with the same immunodeficiency virus strain, suggesting that broad recognition of multiple CD8-TL epitopes should be a key feature of HIV vaccines.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / virology
  • Chronic Disease
  • Haplotypes / genetics
  • Heterozygote*
  • Homozygote
  • Macaca fascicularis / genetics
  • Macaca fascicularis / immunology*
  • Macaca fascicularis / virology*
  • Major Histocompatibility Complex / immunology*
  • Mauritius
  • Molecular Sequence Data
  • Simian Acquired Immunodeficiency Syndrome / complications
  • Simian Acquired Immunodeficiency Syndrome / genetics*
  • Simian Acquired Immunodeficiency Syndrome / immunology*
  • Simian Acquired Immunodeficiency Syndrome / virology
  • Simian Immunodeficiency Virus / genetics
  • Simian Immunodeficiency Virus / immunology*
  • Simian Immunodeficiency Virus / isolation & purification
  • Simian Immunodeficiency Virus / physiology
  • Viremia / complications
  • Viremia / genetics
  • Viremia / immunology
  • Viremia / virology