title: High responsiveness of HLA-B57-restricted Gag-specific CD8+ T cells in vitro may contribute to the protective effect of HLA-B57 in HIV-infection.
abstract: HLA-B57 has been shown to be associated with long-term asymptomatic HIV-1 infection. To investigate the biological mechanism by which the HLA-B57 allele could protect from HIV-1 disease, we studied both the number of CD8(+) T cells as well as CD8(+) T cell responsiveness directed to different HIV-1 Gag peptides presented by HLA-A2, -B8 or -B57. T cells specific for the HLA-B57 peptide KAFSPEVIPMF responded more readily and to a higher extend to antigenic stimulation in vitro than T cells specific for the HLA-A2 peptide SLYNTVATL or the HLA-B8 peptide EIYKRWII. This phenomenon was reproducible with T cells from individuals expressing HLA-B57 in combination with one or both of the other alleles and was persistent during long-term follow-up. Lower reactivity of A2- and B8-restricted T cells was not explained by mutations in the B8- or A2-restricted Gag-peptides. Moreover, no correlation between peptide mutation frequency and IFN-gamma production by the corresponding Gag-specific T cells was observed. In conclusion, functional differences were observed between T cells specific for HIV epitopes derived from the same protein presented by different HLA molecules. B57-restricted KAFSPEVIPMF-specific CD8(+) T cells have relatively high responsiveness, which could contribute to the protective effect of HLA-B57 in HIV infection.
authors.affiliation: Department of Clinical Viro-Immunology, Sanquin Research at CLB & Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1066 CX Amsterdam, The Netherlands.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Jansen
authors.forename: Stefan
authors.initials: S
authors.lastname: Kostense
authors.forename: Kristin
authors.initials: K
authors.lastname: Vandenberghe
authors.forename: Nening M
authors.initials: NM
authors.lastname: Nanlohy
authors.forename: Iris M
authors.initials: IM
authors.lastname: De Cuyper
authors.forename: Erwan
authors.initials: E
authors.lastname: Piriou
authors.forename: Erik H
authors.initials: EH
authors.lastname: Manting
authors.forename: Frank
authors.initials: F
authors.lastname: Miedema
authors.forename: Debbie
authors.initials: D
authors.lastname: van Baarle
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004279:DNA, Viral / Q000235:genetics; D000939:Epitopes / Q000235:genetics; D015683:Gene Products, gag / Q000235:genetics; D053804:Granzymes; D015488:HIV Antigens / Q000235:genetics; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D015789:HLA-A2 Antigen / Q000378:metabolism; D015235:HLA-B Antigens / Q000378:metabolism*; D015795:HLA-B8 Antigen / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000378:metabolism; D009154:Mutation; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012697:Serine Endopeptidases / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism
chemical_list: D004279:DNA, Viral; D000939:Epitopes; D015683:Gene Products, gag; D015488:HIV Antigens; D015789:HLA-A2 Antigen; D015235:HLA-B Antigens; C103707:HLA-B57 antigen; D015795:HLA-B8 Antigen; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D054353:Perforin; D007371:Interferon-gamma; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases