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Clonotype and repertoire changes drive the functional improvement of HIV-specific CD8 T cell populations under conditions of limited antigenic stimulation

Janbazian, Loury, Price, David, Canderan, Glenda, Filali-Mouhim, Abdelali, Asher, Tedi E., Ambrozak, David R., Scheinberg, Phillip, Boulassel, Mohamad Rachid, Routy, Jean-Pierre, Koup, Richard A., Douek, Daniel C., Sekaly, Rafick-Pierre and Trautmann, Lydie 2012. Clonotype and repertoire changes drive the functional improvement of HIV-specific CD8 T cell populations under conditions of limited antigenic stimulation. The Journal of Immunology 188 (3) , pp. 1156-1167. 10.4049/jimmunol.1102610

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Abstract

Persistent exposure to cognate Ag leads to the functional impairment and exhaustion of HIV-specific CD8 T cells. Ag withdrawal, attributable either to antiretroviral treatment or the emergence of epitope escape mutations, causes HIV-specific CD8 T cell responses to wane over time. However, this process does not continue to extinction, and residual CD8 T cells likely play an important role in the control of HIV replication. In this study, we conducted a longitudinal analysis of clonality, phenotype, and function to define the characteristics of HIV-specific CD8 T cell populations that persist under conditions of limited antigenic stimulation. Ag decay was associated with dynamic changes in the TCR repertoire, increased expression of CD45RA and CD127, decreased expression of programmed death-1, and the emergence of polyfunctional HIV-specific CD8 T cells. High-definition analysis of individual clonotypes revealed that the Ag loss-induced gain of function within HIV-specific CD8 T cell populations could be attributed to two nonexclusive mechanisms: 1) functional improvement of persisting clonotypes; and 2) recruitment of particular clonotypes endowed with superior functional capabilities.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QR Microbiology > QR180 Immunology
Publisher: American Association of Immunologists
ISSN: 0022-1767
Last Modified: 04 Jun 2017 04:43
URI: http://orca.cf.ac.uk/id/eprint/43634

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