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-γ 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.