HLA class II-Restricted CD8+ T cells in HIV-1 Virus Controllers

Tinashe E Nyanhete,Kent J Weinhold,Kevin Wiehe,Stephanie A Freel,Tamika Payne,Barton F Haynes,William J Faison,Alyse L Frisbee,Elizabeth Robins,Georgia D Tomaras,M Anthony Moody,Guido Ferrari,Qi-Jing Li,Todd Bradley,Sheetal Sawant

doi:10.1038/s41598-019-46462-8

Tinashe E Nyanhete, Kent J Weinhold + Show 13 more

Open Access

https://doi.org/10.1038/s41598-019-46462-8

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Abstract

A paradigm shifting study demonstrated that induction of MHC class E and II-restricted CD8+ T cells was associated with the clearance of SIV infection in rhesus macaques. Another recent study highlighted the presence of HIV-1-specific class II-restricted CD8+ T cells in HIV-1 patients who naturally control infection (virus controllers; VCs). However, questions regarding class II-restricted CD8+ T cells ontogeny, distribution across different HIV-1 disease states and their role in viral control remain unclear. In this study, we investigated the distribution and anti-viral properties of HLA-DRB1*0701 and DQB1*0501 class II-restricted CD8+ T cells in different HIV-1 patient cohorts; and whether class II-restricted CD8+ T cells represent a unique T cell subset. We show that memory class II-restricted CD8+ T cell responses were more often detectable in VCs than in chronically infected patients, but not in healthy seronegative donors. We also demonstrate that VC CD8+ T cells inhibit virus replication in both a class I- and class II-dependent manner, and that in two VC patients the class II-restricted CD8+ T cells with an anti-viral gene signature expressed both CD4+ and CD8+ T cell lineage-specific genes. These data demonstrated that anti-viral memory class II-restricted CD8+ T cells with hybrid CD4+ and CD8+ features are present during natural HIV-1 infection.

Highlights

There are nearly 37 million people living with HIV-1, and an estimated 1.8 million new HIV-1 infections were reported in 20171
We assessed the distribution of class II-restricted CD8+ T cells in different HIV-1 patient cohorts, their relative contribution towards CD8+ T cell mediated suppression of HIV-1 replication, ontogeny, functional properties and determined T Cell Receptor (TCR)
To further expand on the work done by Ranasinghe et al and investigate whether atypical class II-restricted CD8+ T cells are only present in HIV-1 virus controller (VC), the presence of class II-restricted CD8+ T cells was interrogated in HIV-1 chronic patients, HIV-1 VCs and healthy donors

Summary

Introduction

There are nearly 37 million people living with HIV-1, and an estimated 1.8 million new HIV-1 infections were reported in 20171. Optimism for T cell-based vaccines received a major boost with the report of a non-human primate (NHP) T cell-based vaccine study that resulted in the induction of a novel subset of MHC class II and class E-restricted CD8+ T cells[9,10]. These novel subsets of CD8+ T cells were associated with complete clearance of SIV in 50% of animals[11,12]. Further analysis of elicitation of these atypical CD8+ T cells in humans by other pathogens will elucidate whether they are an attractive target for induction by vaccine strategies

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