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

J Infect Dis. 2005 Nov 1;192(9):1588-96. doi: 10.1086/496894. Epub 2005 Sep 30.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Chronic Disease
  • Female
  • Gene Products, gag / immunology
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / classification
  • HIV-1 / immunology*
  • Humans
  • Lymphocyte Count
  • Male
  • Proteome / immunology
  • Viral Load
  • Viral Proteins / immunology*

Substances

  • Gene Products, gag
  • Proteome
  • Viral Proteins