Role of individual's T cell immunome in controlling HIV-1 progression

Viral and host factors can influence HIV-1 progression, among them Human Leukocyte Antigen (HLA) has shown the strongest effect. However, studies on the functional contribution of HLA in controlling HIV progression toward AIDS are limited by multiple issues, including the viral strain variability within the study subjects. In this study, in a cohort of children infected with a monophyletic strain (CRF02_AG) during an outbreak, we evaluated the HIV-1 Gag, Vif, Vpr, Tat and HCV E1/E2 (as control) proteins circulating in a cohort for the capability to be presented by the HLA molecules in the same population. A total of 70 Non-Progressors and 37 Progressors to AIDS were evaluated. In the presence of a constant capability of HIV-1 to mutate in the region containing epitopes of Gag protein, the number of epitopes recognised in silico by the combination of the HLA alleles along the Gag consensus sequence is significantly higher in the Non-progressors compared with Progressors (HLA-A: Non-progressors=1.532±1.211, Progressors=0.7714±1.031, p=0.0016; HLA-B: Non-progressors=1.556±1.298, Progressors=1.000±0.817, p=0.0319; HLA-DR: Non-progressors=13.30±9.488, Progressors=7.294±6.952, p=0.0006). Similar results were obtained with the other HIV-1 proteins Vif and Vpr, while no differences were obtained in the number of epitopes for HCV E1/E2 protein sequence or for the scrambled HIV-1 sequence. Finally, the results were confirmed also in a subgroup of subjects where both HLA typing and Gag's sequence were available. In conclusion, in absence of bias due to viral strain diversity, it is the overall fitting of the HLA molecules capable of better binding HIV-1 proteins in determining the major role in the control of HIV-1 replication and progression to AIDS. This article is protected by copyright. All rights reserved.