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. © 2005 by the Infectious Diseases Society of America. All rights reserved.