Clonotypic architecture of a Gag-specific CD8+ T-cell response in chronic human HIV-2 infection.
Eur J Immunol
; 51(10): 2485-2500, 2021 10.
Article
em En
| MEDLINE
| ID: mdl-34369597
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Infecções por HIV
/
HIV-2
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Linfócitos T CD8-Positivos
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Especificidade do Receptor de Antígeno de Linfócitos T
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Produtos do Gene gag do Vírus da Imunodeficiência Humana
Tipo de estudo:
Qualitative_research
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article