Journal article
In chronic infection, HIV Gag-Specific CD4+ T cell receptor diversity is higher than CD8+ T cell receptor diversity and is associated with Less HIV quasispecies diversity
Journal of Virology, Vol.95(8), pp.Art. e02380-20
2021
Abstract
Cellular immune responses to Gag correlate with improved HIV control. The full extent of cellular immune responses comprises both the number of epitopes recognized by CD4+ and CD8+ T cells and the diversity of the T cell receptor (TCR) repertoire directed against each epitope. The optimal diversity of the responsive TCR repertoire is unclear. Therefore, we evaluated the TCR diversity of CD4+ and CD8+ T cells responding to HIV-1 Gag to determine if TCR diversity correlates with clinical or virologic metrics. Previous studies of TCR repertoires have been limited primarily to CD8+ T cell responses directed against a small number of well-characterized T cell epitopes restricted by specific human leukocyte antigens. We stimulated peripheral blood mononuclear cells from 21 chronic HIV-infected individuals overnight with a pool of HIV-1 Gag peptides, followed by sorting of activated CD4+ and CD8+ T cells and TCR deep sequencing. We found Gag-reactive CD8+ T cells to be more oligoclonal, with a few dominant TCRs comprising the bulk of the repertoire, compared with the highly diverse TCR repertoires of Gag-reactive CD4+ T cells. HIV sequencing of the same donors revealed that high CD4+ T cell TCR diversity was strongly associated with lower HIV Gag genetic diversity. We conclude that the TCR repertoire of Gag-reactive CD4+ T helper cells displays substantial diversity without a clearly dominant circulating TCR clonotype, in contrast to a hierarchy of dominant TCR clonotypes in the Gag-reactive CD8+ T cells, and may serve to limit HIV diversity during chronic infection.
Details
- Title
- In chronic infection, HIV Gag-Specific CD4+ T cell receptor diversity is higher than CD8+ T cell receptor diversity and is associated with Less HIV quasispecies diversity
- Authors/Creators
- M.A. Pilkinton (Author/Creator) - Vanderbilt University Medical CenterW.J. McDonnell (Author/Creator) - Vanderbilt University Medical CenterL. Barnett (Author/Creator) - Vanderbilt University Medical CenterA. Chopra (Author/Creator) - Murdoch UniversityR. Gangula (Author/Creator) - Vanderbilt University Medical CenterK.D. White (Author/Creator) - Vanderbilt University Medical CenterS. Leary (Author/Creator) - Murdoch UniversityJ. Currenti (Author/Creator) - The University of Western AustraliaS. Gaudieri (Author/Creator) - Murdoch UniversityS.A. Mallal (Author/Creator) - Murdoch UniversityS.A. Kalams (Author/Creator) - Vanderbilt University Medical CenterG. Silvestri (Author/Creator)
- Publication Details
- Journal of Virology, Vol.95(8), pp.Art. e02380-20
- Publisher
- American Society for Microbiology
- Identifiers
- 991005541316407891
- Copyright
- © 2021 American Society for Microbiology
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.6 Immunology
- 1.6.127 T Cell Regulation
- Web Of Science research areas
- Virology
- ESI research areas
- Microbiology