Hierarchical Targeting of Subtype C Human Immunodeficiency Virus Type 1 Proteins by CD8+ T Cells: Correlation with Viral Load

Agatha Masemola, Tumelo Mashishi, Greg Khoury, Phineas Mohube, Pauline Mokgotho, Efthyia Vardas, Mark Colvin, Lynn Zijenah, David Katzenstein, Rosemary Musonda, Susan Allen, Newton Kumwenda, Taha Taha, Glenda Gray, James McIntyre, Salim Abdool Karim, Haynes W. Sheppard, Clive M. Gray

Research output: Contribution to journalArticlepeer-review


An understanding of the relationship between the breadth and magnitude of T-cell epitope responses and viral loads is important for the design of effective vaccines. For this study, we screened a cohort of 46 subtype C human immunodeficiency virus type 1 (HIV-1)-infected individuals for T-cell responses against a panel of peptides corresponding to the complete subtype C genome. We used a gamma interferon ELISPOT assay to explore the hypothesis that patterns of T-cell responses across the expressed HIV-1 genome correlate with viral control. The estimated median time from seroconversion to response for the cohort was 13 months, and the order of cumulative T-cell responses against HIV proteins was as follows: Nef 〉 Gag 〉 Pol 〉 Env 〉 Vif 〉 Rev 〉 Vpr 〉 Tat 〉 Vpu. Nef was the most intensely targeted protein, with 97.5% of the epitopes being clustered within 119 amino acids, constituting almost one-third of the responses across the expressed genome. The second most targeted region was p24, comprising 17% of the responses. There was no correlation between viral load and the breadth of responses, but there was a weak positive correlation (r = 0.297; P = 0.034) between viral load and the total magnitude of responses, implying that the magnitude of T-cell recognition did not contribute to viral control. When hierarchical patterns of recognition were correlated with the viral load, preferential targeting of Gag was significantly (r = 0.445; P = 0.0025) associated with viral control. These data suggest that preferential targeting of Gag epitopes, rather than the breadth or magnitude of the response across the genome, may be an important marker of immune efficacy. These data have significance for the design of vaccines and for interpretation of vaccine-induced responses.

Original languageEnglish (US)
Pages (from-to)3233-3243
Number of pages11
JournalJournal of virology
Issue number7
StatePublished - Apr 2004

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology


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