HIV's evasion of the cellular immune response

Abstract

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 ceils expressing individual MHC class I alietes 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.