Limiting dilution analysis of cytotoxic T lymphocytes to human immunodeficiency virus gag antigens in infected persons: in vitro quantitation of effector cell populations with p17 and p24 specificities.
The presence of cytotoxic T lymphocytes (CTL) to the gag antigens of human immunodeficiency virus (HIV) has been described in infected populations. We found that the majority of this immune response as measured in bulk CTL assays of unstimulated peripheral blood mononuclear cells (PBMC) is directed against the p24 component of the p55 gag precursor protein. Using limiting dilution analysis of this effector cell population we confirm that the majority of activated gag-specific CTL circulating in the PBMC of infected hemophilic patients are directed at p24 determinants and are present at frequencies of 1/36,000 to 1/86,000 lymphocytes. By performing in vitro stimulation after limiting dilution, the precursor population of gag-specific CTL are characterized and quantitated. HIV gag-specific CTL precursors are identified at frequencies of 1/1700 to 1/17,000 lymphocytes and are made up of cells with both p17 and p24 specificities. No HIV gag-specific CTL precursor cells are identified in the PBMC of HIV-uninfected individuals. These studies demonstrate that CTL directed at both p17 and p24 determinants make up the cellular immune repertoire in HIV-infected individuals but that only the p24-specific CTL are routinely found in an activated state in the circulation.
Koup
R A
RA
Department of Pediatrics, University of Massachusetts Medical School, Worcester 01655.
Pikora
C A
CA
Luzuriaga
K
K
Brettler
D B
DB
Day
E S
ES
Mazzara
G P
GP
Sullivan
J L
JL
D016827:CD8 Antigens / Q000032:analysis; D003602:Cytotoxicity, Immunologic; D015683:Gene Products, gag / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology*; D016655:HIV Core Protein p24 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D006679:HIV Seropositivity / Q000276:immunology; D006801:Humans; D011498:Protein Precursors / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus
D016827:CD8 Antigens; D015683:Gene Products, gag; D015488:HIV Antigens; D016655:HIV Core Protein p24; D011498:Protein Precursors; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1; C059767:p55 gag precursor protein, Human immunodeficiency virus 1