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Study of the recognition of HIV-1 Gag and Nef epitopes by T lymphocytes in chronically infected HIV-1 Long-Term Non-Progressors

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Author(s):
Bosco Christiano Maciel da Silva (aut.) [1]
Total Authors: 1
Affiliation:
[1] Universidade de São Paulo (USP). Faculdade de Medicina (FM) - Brasil
Total Affiliations: 1
Document type: Doctoral Thesis
Press: São Paulo. , gráficos, ilustrações, tabelas.
Institution: Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD)
Defense date:
Examining board members:
Dewton de Moraes Vasconcelos; Luís Fernando de Macedo Brigido; Hiro Goto; Claudio Sergio Pannuti; Maria Marluce dos Santos Vilela
Advisor: Dewton de Moraes Vasconcelos
Field of knowledge: Health Sciences - Medicine
Indexed in: Banco de Dados Bibliográficos da USP-DEDALUS; Biblioteca Digital de Teses e Dissertações - USP
Location: Universidade de São Paulo. Biblioteca Central da Faculdade de Medicina; FM W4.DB8 SP.USP FM2; S578est
Abstract

T lymphocytes (T-L) have a paramount role in the control of HIV-1 infection. The responses mediated by these cells against HLA class I epitopes may be associated to the natural protection in long-term non-progressors (LTNP). The literature suggests that some HLA alleles relate to the protection against the immune dysfunction. The aim of this research is to study the recognition of HIV-1 Gag, Nef and RT epitopes by T-L through an ELISPOT IFN-? assay in the peripheral blood mononuclear cells (PBMC) of 24 LTNP selected from French ALT study group. We evaluated the frequency of anti-HIV-1 responses and identified HLA class I epitopes. All individuals presented specific responses to the pools of peptides tested with a median of 5 (2-12). Gag-p24 and Nef were the most frequently recognized proteins. The magnitude of the responses varied from 160 to 12307 SFC/106 PBMC (median=2025). We observed the recognition of 22 epitopes already described in HIV-1 Gag-p17, Gag-p24 and Nef, restricted to HLA class I molecules reported as protective. We have also observed four new epitopes not already described in the literature. Our results suggest that: HIV-1 responses by T-L are present in LTNP; the presence of HLA class I molecules associated with protection in the majority of LTNP are related to the recognition of MHC restricted HIV-1 epitopes; these aspects must be taken into account in the development of a candidate vaccine against HIV-1. (AU)