Costa, Ana I., Koning, Dan, Ladell, Kristin ORCID: https://orcid.org/0000-0002-9856-2938, McLaren, James Edward ORCID: https://orcid.org/0000-0002-7021-5934, Grady, Bart P. X., Schellens, Ingrid M. M., van Ham, Petra, Nijhuis, Monique, Borghans, José A. M., Kesmir, Can, Price, David ORCID: https://orcid.org/0000-0001-9416-2737, van Baarle, Debbie and Silvestri, G. 2015. Complex T-cell receptor repertoire dynamics underlie the CD8+T-cell response to HIV-1. Journal of Virology 89 (1) , pp. 110-119. 10.1128/JVI.01765-14 |
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Abstract
Although CD8 T cells are important for the control of HIV-1 in vivo, the precise correlates of immune efficacy remain unclear. In this study, we conducted a comprehensive analysis of viral sequence variation and T-cell receptor (TCR) repertoire composition across multiple epitope specificities in a group of antiretroviral treatment-naive individuals chronically infected with HIV-1. A negative correlation was detected between changes in antigen-specific TCR repertoire diversity and CD8 T-cell response magnitude, reflecting clonotypic expansions and contractions related to alterations in cognate viral epitope sequences. These patterns were independent of the individual, as evidenced by discordant clonotype-specific transitions directed against different epitopes in single subjects. Moreover, long-term asymptomatic HIV-1 infection was characterized by evolution of the TCR repertoire in parallel with viral replication. Collectively, these data suggest a continuous bidirectional process of adaptation between HIV-1 and virus-specific CD8 T-cell clonotypes orchestrated at the TCR-antigen interface. I
Item Type: | Article |
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Date Type: | Publication |
Status: | Published |
Schools: | Medicine Systems Immunity Research Institute (SIURI) |
Subjects: | R Medicine > R Medicine (General) |
Publisher: | American Society for Microbiology |
ISSN: | 0022-538X |
Date of First Compliant Deposit: | 5 September 2017 |
Date of Acceptance: | 1 October 2014 |
Last Modified: | 04 May 2023 13:21 |
URI: | https://orca.cardiff.ac.uk/id/eprint/85484 |
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