Abstract
ObjectiveTo determine the function and phenotype of CD8+ T-cells targeting consensus and autologous sequences of entire HIV-1 Nef protein.MethodsMultiparameter flow cytometry-based analysis was used to evaluate the responses of two treatment naïve HIV-infected individuals, during primary and the chronic phases of infection.ResultsA greater breadth and magnitude of CD8 IFN-γ responses to autologous compared to clade-B consensus peptides was observed in both subjects. Cross recognition between autologous and consensus peptides decreased in both subjects during progression from primary to chronic infection. The frequencies of TEMRA and TEM CD8+ T-cells targeting autologous peptides were higher than those targeting consensus peptides and were more polyfunctional (IFN-γ+ Gr-B+ CD107a+).ConclusionsOur data indicate superior sensitivity and specificity of autologous peptides. The functional and maturational aspects of “real” versus “cross-recognized” responses were also found to differ, highlighting the importance of a sequence-specific approach towards understanding HIV immune response.
Highlights
A better understanding of the interplay between HIV and the immune system is necessary for the development of a safe and effective HIV vaccine
On follow-up, viremia was shown to increase in one subject (#039) and decrease in the other (#016) subject, heretofore denoted as high viremic (.10,000 copies/ml) and low viremic (,10,000 copies/ml) subjects, respectively
Based on the compositional matrix adjustment method, the percentage of a. a. sequence similarity of autologous HIV-1 Nef with the clade-B consensus Nef varied between 83–85% and 84–85% for the high and low viremic subjects, respectively
Summary
A better understanding of the interplay between HIV and the immune system is necessary for the development of a safe and effective HIV vaccine. Gag and Nef proteins contain the highest density of epitopes recognized by T-cell responses [4,5,6] and HIV-1 Nef, an early viral regulatory protein, is the dominant CD8 T-cell targeted protein during primary HIV infection, while responses to HIV-1 Gag dominate the CD8 T-cell response during the chronic phase [4]. This is not unexpected given that HIV-1 Nef is expressed early in the viral replicative cycle [6] and contains a large number of CTL epitopes [4,7]. The relative contribution of Nef-specific CD8 T-cell responses to the total HIV-induced CD8 T-cell response, decreases early after the HIV infection [8]
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