The selective downregulation of class I major histocompatibility complex proteins by HIV-1 protects HIV-infected cells from NK cells.
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.
Cohen
G B
GB
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Gandhi
R T
RT
Davis
D M
DM
Mandelboim
O
O
Chen
B K
BK
Strominger
J L
JL
Baltimore
D
D
D002478:Cells, Cultured; D003593:Cytoplasm / Q000737:chemistry / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D015536:Down-Regulation / Q000276:immunology*; D015693:Gene Products, nef / Q000502:physiology; D015497:HIV-1 / Q000276:immunology*; D006680:HLA Antigens / Q000502:physiology; D015789:HLA-A2 Antigen / Q000378:metabolism; D015236:HLA-C Antigens / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000821:virology; D054311:nef Gene Products, Human Immunodeficiency Virus; D000097625:HLA-E Antigens
D015693:Gene Products, nef; D006680:HLA Antigens; D015789:HLA-A2 Antigen; D015236:HLA-C Antigens; D015395:Histocompatibility Antigens Class I; D054311:nef Gene Products, Human Immunodeficiency Virus; D000097625:HLA-E Antigens