HIV's evasion of the cellular immune response

Despite a strong cytotoxic T-lymphocyte (CTL) response directed against vir al antigens, untreated individuals infected with the human immunodeficiency virus (HIV-1) develop AIDS. We have found that primary T cells infected wi th HIV-1 downregulate surface MHC class I antigens and are resistant to lys is by HLA-A2-restricted CTL clones. In contrast, cells infected with an HIV -1 in which the nei gene is disrupted are sensitive to CTLs in an MHC and p eptide-specific manner. In primary T cells HLA-A2 antigens are downmodulate d more dramatically than total MHC class I antigens, suggesting that nef se lectively downmodulates certain MHC class I antigens. In support of this, s tudies on cells expressing individual MHC class I alleles have revealed tha t nef does not downmodulate HLA-C and HLA-E antigens. This selective downmo dulation allows infected cells to maintain resistance to certain natural ki ller cells that lyse infected cells expressing low levels of MHC class I an tigens. Downmodulation of MHC class I HLA-A2 antigens occurs not only in pr imary T cells, but also in B and astrocytoma cell lines. No effect of other HIV-1 accessory proteins such as vpu and vpr was observed. Thus Nef is a p rotein that may promote escape of HIV-1 from immune surveillance.