The selective downregulation of class I major histocompatibility complex proteins by HIV-1 protects HIV-infected cells from NK cells

Immunity. 1999 Jun;10(6):661-71. doi: 10.1016/s1074-7613(00)80065-5.


To avoid detection by CTL, HIV encodes mechanisms for removal of class I MHC proteins from the surface of infected cells. However, class I downregulation potentially exposes the virus-infected cell to attack by NK cells. Human lymphoid cells are protected from NK cell cytotoxicity primarily by HLA-C and HLA-E. We present evidence that HIV-1 selectively downregulates HLA-A and HLA-B but does not significantly affect HLA-C or HLA-E. We then identify the residues in HLA-C and HLA-E that protect them from HIV down-regulation. This selective downregulation allows HIV-infected cells to avoid NK cell-mediated lysis and may represent for HIV a balance between escape from CTL and maintenance of protection from NK cells. These results suggest that subpopulations of CTL and NK cells may be uniquely suited for combating HIV.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cells, Cultured
  • Cytoplasm / chemistry
  • Cytoplasm / immunology
  • Cytotoxicity, Immunologic
  • Down-Regulation / immunology*
  • Gene Products, nef / physiology
  • HIV-1 / immunology*
  • HLA Antigens / physiology
  • HLA-A2 Antigen / metabolism
  • HLA-C Antigens / physiology
  • Histocompatibility Antigens Class I / chemistry
  • Histocompatibility Antigens Class I / immunology*
  • Histocompatibility Antigens Class I / physiology
  • Humans
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / virology
  • nef Gene Products, Human Immunodeficiency Virus


  • Gene Products, nef
  • HLA Antigens
  • HLA-A2 Antigen
  • HLA-C Antigens
  • HLA-E antigen
  • Histocompatibility Antigens Class I
  • nef Gene Products, Human Immunodeficiency Virus