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The dynamics of T-cell receptor (TCR) selection in chronic HIV-1 infection, and its association with clinical outcome, is well documented for an array of MHC-peptide complexes and disease stages. However, the factors that may contribute to the selection and expansion of CD8+ T-cells in chronic HIV-2 infection, especially at clonal level remain unclear. To address this question, we undertook a detailed molecular characterization of the clonotypic architecture of an HLA-B*3501 restricted Gag -specific CD8+ T-cell response in donors chronically infected with HIV-2 using a combination of flow cytometry, tetramer-specific CD8+ TCR clonotyping and in vitro assays. We show that the response to the NY9 epitope is hierarchical and narrow in terms of T-cell receptor alpha (TCRA) and beta (TCRB) gene usage yet clonotypically diverse. Furthermore, clonotypic dominance in shared origin cytotoxic T lymphocyte (CTL) clones was associated with a greater magnitude of cytokine production and antigen sensitivity at limiting antigen dilution as well as enhanced cross-reactivity for known HIV-2 variants. Hence, our data suggest that effector mobilization and expansion in human chronic HIV-2 infection may be linked to the qualitative features of specific CD8+ T-cell clonotypes, which could have implications for viral control and disease outcome. This article is protected by copyright. All rights reserved.

Original publication

DOI

10.1002/eji.202048931

Type

Journal article

Journal

European journal of immunology

Publication Date

09/08/2021

Addresses

Tissue Analysis Core, Vaccine Research Centre, Bethesda, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.