title: HIV-1 Nef protein protects infected primary cells against killing by cytotoxic T lymphocytes.
abstract: 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.
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Collins
authors.forename: B K
authors.initials: BK
authors.lastname: Chen
authors.forename: S A
authors.initials: SA
authors.lastname: Kalams
authors.forename: B D
authors.initials: BD
authors.lastname: Walker
authors.forename: D
authors.initials: D
authors.lastname: Baltimore
mesh_terms: 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
chemical_list: D018984:Epitopes, T-Lymphocyte; D015693:Gene Products, nef; D015789:HLA-A2 Antigen; D054311:nef Gene Products, Human Immunodeficiency Virus; D000469:Alkaline Phosphatase