title: Efficient lysis of human immunodeficiency virus type 1-infected cells by cytotoxic T lymphocytes.
abstract: Numerous studies of human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T lymphocytes (CTL) have examined their ability to recognize B-cell lines expressing recombinant HIV-1 proteins, but relatively few data regarding the lysis of HIV-1-infected cells by CTL are available. We studied the ability of HIV-1-specific CTL clones of defined epitope specificity and HLA restriction to lyse infected CD4+ cells at serial time points following infection. CD4+ cell lines were acutely infected with HIV-1 IIIB at a high multiplicity of infection, and the kinetics of cell lysis were examined and compared with the kinetics of viral replication. Intracellular HIV-1 p24 expression was detected by 1 to 2 days after infection, reaching over 98% positive cells by day 4. Recognition of the infected cells by HLA A2- and B14-restricted CTL clones closely paralleled intracellular p24 expression and preceded peak virion production. The maximal levels of lysis with Gag-, reverse transcriptase-, and envelope-specific clones were different, however. The Gag- and envelope-specific clones lysed infected cells at levels equivalent to peptide-sensitized controls, whereas lysis by the reverse transcriptase-specific clones plateaued at a lower level. Peptide titration curves indicated that this effect was not due to differences in sensitivity to the cognate epitopes for the different clones. Although HIV-1 infection induced an approximately 50% decrease in class I HLA expression on the surface of infected cells, lysis by CTL clones was unaffected. These studies indicate that HIV-1-specific CTL can efficiently lyse HIV-1-infected CD4+ cells and suggest that the partial downregulation of class I molecules in infected cells does not significantly affect recognition by CTL.
authors.affiliation: AIDS Research Center, Massachusetts General Hospital, Charlestown 02129, USA.
authors.forename: O O
authors.initials: OO
authors.lastname: Yang
authors.forename: S A
authors.initials: SA
authors.lastname: Kalams
authors.forename: M
authors.initials: M
authors.lastname: Rosenzweig
authors.forename: A
authors.initials: A
authors.lastname: Trocha
authors.forename: N
authors.initials: N
authors.lastname: Jones
authors.forename: M
authors.initials: M
authors.lastname: Koziel
authors.forename: B D
authors.initials: BD
authors.lastname: Walker
authors.forename: R P
authors.initials: RP
authors.lastname: Johnson
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000595:Amino Acid Sequence; D000906:Antibodies; D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D005434:Flow Cytometry; D015683:Gene Products, gag / Q000737:chemistry / Q000276:immunology; D016655:HIV Core Protein p24 / Q000096:biosynthesis / Q000276:immunology; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D015789:HLA-A2 Antigen / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology; D059909:HLA-B14 Antigen; D006801:Humans; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014779:Virus Replication
chemical_list: D000906:Antibodies; D000939:Epitopes; D015683:Gene Products, gag; D016655:HIV Core Protein p24; D015789:HLA-A2 Antigen; D015235:HLA-B Antigens; D059909:HLA-B14 Antigen; D009842:Oligopeptides