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.