Profile of T Cell Recognition of HIV Type 1 Consensus Group M Gag and Nef Peptides in a Clade A1- and D-Infected Ugandan Population
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Date
2012
Journal Title
Journal ISSN
Volume Title
Publisher
AIDS research and human retroviruses
Abstract
Reagents for evaluating non-clade B HIV-specific T cell responses are uncommon. Peptides based on highly
conserved HIV-1 consensus group M sequences that are phylogenetically closer to most circulating strains may
provide potential alternative reagents in populations with diverse infections, and may be relevant for vaccine
design. Recognition of such reagents in clade A1-and D-infected populations has not been previously evaluated.
Interferon (IFN)-c ELISpot assay was used to evaluate T cell recognition of Gag and Nef peptides based on
consensus group M sequences in 50 treatment-naive adults predominantly infected with HIV-1 clades A1 and D.
Gag-induced T cell responses were correlated with gag sequence diversity. Infecting clades were determined
from gag sequences for 45 of the 50 subjects as 40% clade A1 (18/45), 45% clade D (20/45), 2% clade C (1/45), 2%
A1/C recombinant (1/45), 2% A1/D (1/45), 7% CRF10_CD (3/45), and 2% U (unclassifiable) (1/45). The mean
genetic divergence and diversity of clade A and D gag region compared to group M consensus sequences at
synonymous and nonsynonymous nucleotide and amino acid levels were not always significant. Gag peptides
were targeted at significantly higher frequency [88% (44/50)] than Nef [64% (32/50)]; p = 0.014, although their
mean IFN-c magnitudes were comparable ([3703 (95% CI 2567–4839)] vs. [2120 (95% CI 478–3762)]), respectively.
Measurable virus-induced IFN-c responses were detected in 96% (48/50) individuals, primarily targeting the
more conserved Gag p24 and Nef central core regions. Use of these reagents to screen for HIV-specific IFN-c
responses may mitigate the challenge of viral diversity; although this targeting is apparently biased toward a
few highly conserved epitopes.
Description
Keywords
T Cell, HIV, Nef Peptides, Clade A1-, Ugandan Population
Citation
Serwanga, J., Mugaba, S., Pimego, E., Nanteza, B., Lyagoba, F., Nakubulwa, S., ... & Kaleebu, P. (2012). Profile of T cell recognition of HIV type 1 consensus group M Gag and Nef peptides in a clade A1-and D-infected Ugandan population. AIDS research and human retroviruses, 28(4), 384-392. DOI: 10.1089/aid.2011.0175