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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, McLaren, James Edward, Grady, Bart P. X., Schellens, Ingrid M. M., van Ham, Petra, Nijhuis, Monique, Borghans, José A. M., Kesmir, Can, Price, David, 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
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: 12 Jun 2019 09:36
URI: http://orca.cf.ac.uk/id/eprint/85484

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