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Abstract
IDENTIFICATION OF HIV-SPECIFIC CD4+ T CELLS IN PERIPHERAL BLOOD OF HIV-1- INFECTED INDIVIDUALS BY TETRAMERIC HLA-DR MOLECULES COVALENTLY COMPLEXED WITH PEPTIDES.
YASSINE DIAB B, YOUNES S, BRETON G, MACDONALD K, ROUTY J, CONNORS M, SEKALY R
State object of study: Previous reports have demonstrated the presence of potent HIV-specific responses in primary HIV infection (PI), which were maintained either in long-term non-progressors (LTNP) or in individuals treated with highly active anti-retroviral therapy (HAART). The major goals of this work were to characterize the origin of HIV-specific CD4+ T cells and to identify their role in disease progression.
Materials and methods: In order to directly assess the HIV-specific CD4+ T cell response in HIV+ individuals, we used an approach based on the construction of 5 soluble tetrameric HLA-DR molecules covalently linked to 8 immunogenic and conserved HIV peptides (derived from p24, gp120, and RT51).
Results: HLA-DRB1 typing by PCR-SSP was performed on 100 patients of two cohorts including PI patients and LTNP individuals. HIV-specific class II tetramers are being used to monitor the HIV-specific CD4+ T cell responses in these cohorts, and results will be presented. A considerable specific proliferation has been observed in LTNP patients for the p51-11 peptide but not for the other peptides tested. In all tested PI HAART-treated patients, the p24-5 peptide is the most recognized epitope while the p24-1 peptide induces only a slight proliferative response in some of the patients. In contrast, the p24-3 peptide induces a strong immunodominant HIV-specific CD4+ T cell proliferation response in untreated progressors at early stages of infection. However, this response rapidly disappears without subsequent clinical progression of disease (undetectable viral load) and is replaced by slight recognitions of p24-5 and p24-8.
Conclusions: Our preliminary results suggest that the most specific T helper cells have been either deleted or anergized early in the course of infection. Greater characterization of the specificity of HIV-directed CD4+ T cells will allow the identification of candidate HIV-derived T helper epitopes to be used in peptide-based vaccines.
The 1st. IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
11
Suggested Citation
"YASSINEDIABB, et al.
IDENTIFICATION OF HIV-SPECIFIC CD4+ T CELLS IN PERIPHERAL BLOOD OF HIV-1- INFECTED INDIVIDUALS BY TETRAMERIC HLA-DR MOLECULES COVALENTLY COMPLEXED WITH PEPTIDES..
Oral Presentation:
The 1st. IAS Conference on HIV Pathogenesis and Treatment
:
Abstract no.
11"
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