期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 51, 期 10, 页码 2485-2500出版社
WILEY
DOI: 10.1002/eji.202048931
关键词
CTL; Gag; HIV-2; TCR repertoire
类别
资金
- MRC Unit
- MRC Laboratories in the Gambia
- MRC [G0801751]
- Harold Hyam Wingate Foundation
- MRC [G0801751, MR/L018942/1] Funding Source: UKRI
The study reveals that the qualitative features of specific CD8+ T-cell clonotypes may be linked to effector mobilization and expansion in chronic HIV-2 infection, potentially impacting viral control and disease outcome.
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.
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