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 MH C proteins from the surface of infected cells. However, class I downregulat ion potentially exposes the virus-infected cell to attack by NK cells. Huma n 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 identif y the residues in HLA-C and HLA-E that protect them from HIV downregulation . 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 sub populations of CTL and NK cells may be uniquely suited for combating HIV.