HIV-1 Subtype C gag-specific T-cell responses in relation to human leukocyte antigens in a diverse population of HIV-infected Ethiopians.
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.
Tsegaye
Aster
A
Ethiopian-Netherlands AIDS Research Project, Ethiopian Health and Nutrition Research Institute, Addis Ababa, Ethiopia.
Ran
Leonie
L
Wolday
Dawit
D
Petros
Beyene
B
Dorigo
Wendelien
W
Piriou
Erwan
E
Messele
Tsehaynesh
T
Sanders
Eduard
E
Tilahun
Tesfaye
T
Eshetu
Deresse
D
Schuitemaker
Hanneke
H
Coutinho
Roel A
RA
Miedema
Frank
F
Borghans
José
J
van Baarle
Debbie
D
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
D015683:Gene Products, gag; D010455:Peptides