HIV-1 Subtype C gag-specific T-cell responses in relation to human leukocyte antigens in a diverse population of HIV-infected Ethiopians.
Tsegaye A., Ran L., Wolday D., Petros B., Dorigo W., Piriou E., Messele T., Sanders E., Tilahun T., Eshetu D., Schuitemaker H., Coutinho RA., Miedema F., Borghans J., van Baarle D.
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.