Polyfunctional CD8+ T-Cell Response to Autologous Peptides from Protease and Reverse Transcriptase of HIV-1 Clade B

Author(s): Liliana Acevedo-Saenz, Federico Perdomo-Celis, Carlos J. Montoya, Paula A. Velilla*.

Journal Name: Current HIV Research

Volume 17 , Issue 5 , 2019

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Graphical Abstract:


Background: The diversity of the HIV proteome influences the cellular response and development of an effective vaccine, particularly due to the generation of viral variants with mutations located within CD8+ T-cell epitopes. These mutations can affect the recognition of the epitopes, that may result in the selection of HIV variants with mutated epitopes (autologous epitopes) and different CD8+ T-cell functional profiles.

Objective: To determine the phenotype and functionality of CD8+ T-cell from HIV-infected Colombian patients in response to autologous and consensus peptides derived from HIV-1 clade B protease and reverse transcriptase (RT).

Methods: By flow cytometry, we compared the ex vivo CD8+ T-cell responses from HIV-infected patients to autologous and consensus peptides derived from HIV-1 clade B protease and RT, restricted by HLA-B*35, HLA-B*44 and HLA-B*51 alleles.

Results: Although autologous peptides restricted by HLA-B*35 and HLA-B*44 did not show any differences compared with consensus peptides, we observed the induction of a higher polyfunctional profile of CD8+ T-cells by autologous peptides restricted by HLA-B*51, particularly by the production of interferon-γ and macrophage inflammatory protein-1β. The response by different memory CD8+ T-cell populations was comparable between autologous vs. consensus peptides. In addition, the magnitude of the polyfunctional response induced by the HLA-B*51-restricted QRPLVTIRI autologous epitope correlated with low viremia.

Conclusion: Autologous peptides should be considered for the evaluation of HIV-specific CD8+ Tcell responses and to reveal some relevant epitopes that could be useful for therapeutic strategies aiming to promote polyfunctional CD8+ T-cell responses in a specific population of HIV-infected patients.

Keywords: HIV, CD8+ T-cells, protease, reverse transcriptase, HLA-B, autologous, consensus.

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Year: 2019
Page: [350 - 359]
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DOI: 10.2174/1570162X17666191017105910
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