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  • Title: Differential immunogenicity of HIV-1 clade C proteins in eliciting CD8+ and CD4+ cell responses.
    Author: Ramduth D, Chetty P, Mngquandaniso NC, Nene N, Harlow JD, Honeyborne I, Ntumba N, Gappoo S, Henry C, Jeena P, Addo MM, Altfeld M, Brander C, Day C, Coovadia H, Kiepiela P, Goulder P, Walker B.
    Journal: J Infect Dis; 2005 Nov 01; 192(9):1588-96. PubMed ID: 16206073.
    Abstract:
    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.
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