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Complex T-cell receptor repertoire dynamics underlie the CD8+T-cell response to HIV-1

Costa, Ana I., Koning, Dan, Ladell, Kristin ORCID:, McLaren, James Edward ORCID:, Grady, Bart P. X., Schellens, Ingrid M. M., van Ham, Petra, Nijhuis, Monique, Borghans, José A. M., Kesmir, Can, Price, David ORCID:, 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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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
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

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