Differential immunogenicity of HIV-1 clade C proteins in eliciting CD8+ and CD4+ cell responses

Background. The relative immunogenicity of human immunodeficiency virus type 1 (HIV-1) proteins for CD8(+) and CD4(+) cell responses has not been defined. Methods. HIV- 1 - specific T cell responses were evaluated in 65 chronically HIV- 1 - infected untreated subjects by interferon-gamma flow cytometry with peptides spanning the clade C consensus sequence. Results. The magnitude of HIV- 1 - specific CD8(+) T cell responses correlated significantly with CD4(+) cell responses, but the percentage of CD8(+) T cells directed against HIV-1 (median, 2.76%) was always greater than that of CD4(+) cells ( median, 0.24%). Although CD8(+) T cell responses were equally distributed among Gag, Pol, and the regulatory and accessory proteins, Gag was the dominant target for CD4(+) cell responses. There was no consistent relationship between virus-specific CD8(+) or CD4(+) cell response and viral load. However, the median viral load in subjects in whom Gag was the dominant CD8(+) T cell target was significantly lower than that in subjects in whom non-Gag proteins were the main target (P =.007). Conclusions. Gag-specific responses dominate the CD4(+) T cell response to HIV, whereas CD8(+) T cell responses are broadly distributed, which indicates differential immunogenicity of these cells against HIV-1. The preferential targeting of Gag by CD8(+) T cells is associated with enhanced control of viral load.