Clonotypic architecture of a Gag-specific CD8+ T-cell response in chronic human HIV-2 infection.

Moysi E., Darko S., Gea-Mallorquí E., Petrovas C., Almeida JR., Wolinsky D., Peng Y., Jaye A., Stewart-Jones G., Douek DC., Koup RA., Dong T., Rowland-Jones S.

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 the 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 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.

DOI

10.1002/eji.202048931

Type

Journal article

Journal

European journal of immunology

Publication Date

10/2021

Volume

51

Pages

2485 - 2500

Addresses

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

Keywords

CD8-Positive T-Lymphocytes, Humans, HIV-2, HIV Infections, Chronic Disease, Receptors, Antigen, T-Cell, alpha-beta, Epitopes, T-Lymphocyte, Lymphocyte Activation, T-Cell Antigen Receptor Specificity, Amino Acid Motifs, Conserved Sequence, gag Gene Products, Human Immunodeficiency Virus, Host-Pathogen Interactions

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