HIV-1 Nef protein protects infected primary cells against killing by cytotoxic T lymphocytes

Nature. 1998 Jan 22;391(6665):397-401. doi: 10.1038/34929.


Cytotoxic T lymphocytes (CTLs) lyse virally infected cells that display viral peptide epitopes in association with major histocompatibility complex (MHC) class I molecules on the cell surface. However, despite a strong CTL response directed against viral epitopes, untreated people infected with the human immunodeficiency virus (HIV-1) develop AIDS. To resolve this enigma, we have examined the ability of CTLs to recognize and kill infected primary T lymphocytes. We found that CTLs inefficiently lysed primary cells infected with HIV-1 if the viral nef gene product was expressed. Resistance of infected cells to CTL killing correlated with nef-mediated downregulation of MHC class I and could be overcome by adding an excess of the relevant HIV-1 epitope as soluble peptide. Thus, Nef protected infected cells by reducing the epitope density on their surface. This effect of nef may allow evasion of CTL lysis by HIV-1-infected cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkaline Phosphatase / genetics
  • Alkaline Phosphatase / metabolism
  • Cell Death
  • Cells, Cultured
  • Clone Cells
  • Cytotoxicity, Immunologic
  • Epitopes, T-Lymphocyte / immunology
  • Gene Products, nef / genetics
  • Gene Products, nef / immunology*
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • HLA-A2 Antigen / immunology
  • Humans
  • T-Lymphocytes / immunology
  • T-Lymphocytes / virology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • nef Gene Products, Human Immunodeficiency Virus


  • Epitopes, T-Lymphocyte
  • Gene Products, nef
  • HLA-A2 Antigen
  • nef Gene Products, Human Immunodeficiency Virus
  • Alkaline Phosphatase