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

Loury Janbazian, David A. Price, Glenda Canderan, Abdelali Filali-Mouhim, Tedi E. Asher, David R. Ambrozak, Phillip Scheinberg, Mohamad Rachid Boulassel, Jean Pierre Routy, Richard A. Koup, Daniel C. Douek, Rafick Pierre Sekaly, Lydie Trautmann

Research output: Contribution to journalArticle

27 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1156-1167
Number of pages12
JournalJournal of Immunology
Volume188
Issue number3
DOIs
Publication statusPublished - Feb 1 2012

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HIV
T-Lymphocytes
Population
Epitopes
Phenotype
Mutation

ASJC Scopus subject areas

  • Immunology

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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 A.; 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; Trautmann, Lydie.

In: Journal of Immunology, Vol. 188, No. 3, 01.02.2012, p. 1156-1167.

Research output: Contribution to journalArticle

Janbazian, L, Price, DA, Canderan, G, Filali-Mouhim, A, Asher, TE, Ambrozak, DR, Scheinberg, P, Boulassel, MR, Routy, JP, Koup, RA, Douek, DC, Sekaly, RP & Trautmann, L 2012, 'Clonotype and repertoire changes drive the functional improvement of HIV-specific CD8 T cell populations under conditions of limited antigenic stimulation', Journal of Immunology, vol. 188, no. 3, pp. 1156-1167. https://doi.org/10.4049/jimmunol.1102610
Janbazian, Loury ; Price, David A. ; 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 ; Trautmann, Lydie. / Clonotype and repertoire changes drive the functional improvement of HIV-specific CD8 T cell populations under conditions of limited antigenic stimulation. In: Journal of Immunology. 2012 ; Vol. 188, No. 3. pp. 1156-1167.
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