HIV-1 Nef protein protects infected primary cells against killing by cytotoxic T lymphocytes.
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.
Collins
K L
KL
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Chen
B K
BK
Kalams
S A
SA
Walker
B D
BD
Baltimore
D
D
D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D016923:Cell Death; D002478:Cells, Cultured; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015693:Gene Products, nef / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D054311:nef Gene Products, Human Immunodeficiency Virus
D018984:Epitopes, T-Lymphocyte; D015693:Gene Products, nef; D015789:HLA-A2 Antigen; D054311:nef Gene Products, Human Immunodeficiency Virus; D000469:Alkaline Phosphatase