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Author Notes:

Danni Ramduth: dramduth@gmail.com

Conceived and designed the experiments: DR CLD PG BDW.

Performed the experiments: DR CFT NM CdP SR MvdS ZM KN ESM.

Analyzed the data: DR CLD CdP PK PG BDW.

Contributed reagents/materials/analysis tools: DEK.

Wrote the paper: DR CLD CdP HS HMC BDW.

We thank the subjects and staff, in particular Kesia Mgwenya and Nokuthula at The Sinikithemba Support Group at McCords Hospital in Durban.

The authors have declared that no competing interests exist.

Subject:

Research Funding:

This study was funded by the US National Institute of Health (Contract N01-A1-15422, 2 RO1AI46995-06, and RO1AI067073).

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics

Immunodominant HIV-1 Cd4+T Cell Epitopes in Chronic Untreated Clade C HIV-1 Infection

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Journal Title:

PLoS ONE

Volume:

Volume 4, Number 4

Publisher:

, Pages e5013-e5013

Type of Work:

Article | Final Publisher PDF

Abstract:

Background: A dominance of Gag-specific CD8+ T cell responses is significantly associated with a lower viral load in individuals with chronic, untreated clade C human immunodeficiency virus type 1 (HIV-1) infection. This association has not been investigated in terms of Gag-specific CD4+ T cell responses, nor have clade C HIV-1-specific CD4+ T cell epitopes, likely a vital component of an effective global HIV-1 vaccine, been identified. Methodology/Principal Findings: Intracellular cytokine staining was conducted on 373 subjects with chronic, untreated clade C infection to assess interferon-gamma (IFN-c) responses by CD4+ T cells to pooled Gag peptides and to determine their association with viral load and CD4 count. Gag-specific IFN-γ-producing CD4+ T cell responses were detected in 261/373 (70%) subjects, with the Gag responders having a significantly lower viral load and higher CD4 count than those with no detectable Gag response (p<0.0001 for both parameters). To identify individual peptides targeted by HIV-1-specific CD4+ T cells, separate ELISPOT screening was conducted on CD8-depleted PBMCs from 32 chronically infected untreated subjects, using pools of overlapping peptides that spanned the entire HIV-1 clade C consensus sequence, and reconfirmed by flow cytometry to be CD4+ mediated. The ELISPOT screening identified 33 CD4+ peptides targeted by 18/32 patients (56%), with 27 of the 33 peptides located in the Gag region. Although the breadth of the CD4+ responses correlated inversely with viral load (p = 0.015), the magnitude of the response was not significantly associated with viral load. Conclusions/Significance: These data indicate that in chronic untreated clade C HIV-1 infection, IFN-γ-secreting Gag-specific CD4+ T cell responses are immunodominant, directed at multiple distinct epitopes, and associated with viral control.

Copyright information:

© 2009 Ramduth et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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