title: CD8+ T cell responses to human immunodeficiency viruses type 2 (HIV-2) and type 1 (HIV-1) gag proteins are distinguishable by magnitude and breadth but not cellular phenotype.
abstract: The mechanisms underlying the relatively slow progression of human immunodeficiency virus type 2 (HIV-2) compared with HIV-1 infection are undefined and could be a result of more effective immune responses. We used HIV-2 and HIV-1 IFN-gamma enzyme-linked immunospot assays to evaluate CD8(+) T cell responses in antiretroviral-naive HIV-2- ('HIV-2(+)') and HIV-1-infected ('HIV-1(+)') individuals. Gag-specific responses were detected in the majority of HIV-2(+) and HIV-1(+) subjects. Overlapping gag peptide analysis indicated a significantly greater magnitude and breadth of responses in the HIV-1(+) cohort, and this difference was attributable to low responses in HIV-2(+) subjects with undetectable viral load (medians 2107 and 512 spot-forming units per 10(6) PBMC, respectively, p=0.007). We investigated the phenotype of viral epitope-specific CD8(+) T cells identified with HLA-B53- and HLA-B58-peptide tetramers (8 HIV-2(+), 11 HIV-1(+) subjects). HIV-2-specific CD8(+) T cells were predominantly CD27(+) CD45RA(-), and only a minority expressed perforin. The limited breadth and low frequency of CD8(+) T cell responses to HIV-2 gag in aviremic HIV-2(+) subjects suggests that these responses reflect antigen load in plasma, as is the case in HIV-1 infection. Immune control of HIV-2 does not appear to be related to the frequency of perforin-expressing virus-specific CD8(+) T cells.
authors.affiliation: MRC Human Immunology Group, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
authors.forename: Geraldine M A
authors.initials: GM
authors.lastname: Gillespie
authors.forename: Susana
authors.initials: S
authors.lastname: Pinheiro
authors.forename: Mohammad
authors.initials: M
authors.lastname: Sayeid-Al-Jamee
authors.forename: Abraham
authors.initials: A
authors.lastname: Alabi
authors.forename: Steve
authors.initials: S
authors.lastname: Kaye
authors.forename: Sehu
authors.initials: S
authors.lastname: Sabally
authors.forename: Ramu
authors.initials: R
authors.lastname: Sarge-Njie
authors.forename: Harr
authors.initials: H
authors.lastname: Njai
authors.forename: Ken
authors.initials: K
authors.lastname: Joof
authors.forename: Assan
authors.initials: A
authors.lastname: Jaye
authors.forename: Hilton
authors.initials: H
authors.lastname: Whittle
authors.forename: Sarah
authors.initials: S
authors.lastname: Rowland-Jones
authors.forename: Lucy
authors.initials: L
authors.lastname: Dorrell
mesh_terms: D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology*; D015488:HIV Antigens; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D015498:HIV-2 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology; D008969:Molecular Sequence Data; D054353:Perforin; D010641:Phenotype; D052899:Pore Forming Cytotoxic Proteins; D019562:Viral Load
chemical_list: D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D015488:HIV Antigens; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D007371:Interferon-gamma