HIV's evasion of the cellular immune response.
Despite a strong cytotoxic T-lymphocyte (CTL) response directed against viral antigens, untreated individuals infected with the human immunodeficiency virus (HIV-1) develop AIDS. We have found that primary T cells infected with HIV-1 downregulate surface MHC class I antigens and are resistant to lysis by HLA-A2-restricted CTL clones. In contrast, cells infected with an HIV-1 in which the nef gene is disrupted are sensitive to CTLs in an MHC and peptide-specific manner. In primary T cells HLA-A2 antigens are downmodulated more dramatically than total MHC class I antigens, suggesting that nef selectively downmodulates certain MHC class I antigens. In support of this, studies on cells expressing individual MHC class I alleles have revealed that nef does not downmodulate HLA-C and HLA-E antigens. This selective downmodulation allows infected cells to maintain resistance to certain natural killer cells that lyse infected cells expressing low levels of MHC class I antigens. Downmodulation of MHC class I HLA-A2 antigens occurs not only in primary 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 protein that may promote escape of HIV-1 from immune surveillance.
Collins
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KL
Department of Medicine, University of Michigan, Ann Arbor, USA.
Baltimore
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D000818:Animals; D015683:Gene Products, gag / Q000276:immunology; D015693:Gene Products, nef / Q000276:immunology; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013997:Time Factors; D054311:nef Gene Products, Human Immunodeficiency Virus
D015683:Gene Products, gag; D015693:Gene Products, nef; D015395:Histocompatibility Antigens Class I; D054311:nef Gene Products, Human Immunodeficiency Virus