title: HIV-1 Subtype C gag-specific T-cell responses in relation to human leukocyte antigens in a diverse population of HIV-infected Ethiopians.
abstract: Knowledge of the most dominant T-cell epitopes in the context of the local human leukocyte antigen (HLA) background is a prerequisite for the development of an effective HIV vaccine. In 100 Ethiopian subjects, 16 different HLA-A, 23 HLA-B, and 12 HLA-C specificities were observed. Ninety-four percent of the population carried at least 1 of the 5 most common HLA-A and/or HLA-B specificities. HIV-specific T-cell responses were measured in 48 HIV-infected Ethiopian subjects representing a wide range of ethnicities in Ethiopia using the interferon (IFN)-gamma enzyme-linked immunospot (Elispot) assay and 49 clade C-specific synthetic Gag peptides. Fifty-eight percent of the HIV-positive study subjects showed T-cell responses directed to 1 or more HIV Gag peptides. Most Gag-specific responses were directed against the subset of peptides spanning Gag p24. The breadth of response ranged from 1 to 9 peptides, with most (78%) individuals showing detectable responses to <3 Gag peptides. The magnitude of HIV-specific T-cell responses was not associated with HIV viral load but correlated positively with CD4 T-cell counts. The most frequently targeted Gag peptides overlapped with those previously described for HIV-1 subtype C-infected southern Africans, and therefore can be used in a multiethnic vaccine.
authors.affiliation: Ethiopian-Netherlands AIDS Research Project, Ethiopian Health and Nutrition Research Institute, Addis Ababa, Ethiopia.
authors.forename: Aster
authors.initials: A
authors.lastname: Tsegaye
authors.forename: Leonie
authors.initials: L
authors.lastname: Ran
authors.forename: Dawit
authors.initials: D
authors.lastname: Wolday
authors.forename: Beyene
authors.initials: B
authors.lastname: Petros
authors.forename: Wendelien
authors.initials: W
authors.lastname: Dorigo
authors.forename: Erwan
authors.initials: E
authors.lastname: Piriou
authors.forename: Tsehaynesh
authors.initials: T
authors.lastname: Messele
authors.forename: Eduard
authors.initials: E
authors.lastname: Sanders
authors.forename: Tesfaye
authors.initials: T
authors.lastname: Tilahun
authors.forename: Deresse
authors.initials: D
authors.lastname: Eshetu
authors.forename: Hanneke
authors.initials: H
authors.lastname: Schuitemaker
authors.forename: Roel A
authors.initials: RA
authors.lastname: Coutinho
authors.forename: Frank
authors.initials: F
authors.lastname: Miedema
authors.forename: José
authors.initials: J
authors.lastname: Borghans
authors.forename: Debbie
authors.initials: D
authors.lastname: van Baarle
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005002:Ethiopia / Q000453:epidemiology; D005260:Female; D015683:Gene Products, gag / Q000737:chemistry / Q000276:immunology*; D015658:HIV Infections / Q000453:epidemiology / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000145:classification* / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology
chemical_list: D015683:Gene Products, gag; D010455:Peptides