Clonotype and repertoire changes drive the functional improvement of HIV-specific CD8 T cell populations under conditions of limited antigenic stimulation.
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.
Laboratory of Immunology, Department of Microbiology and Immunology, University of Montreal, Montreal, Quebec H2X 1P1, Canada.
Loury
L
Janbazian
David A
DA
Price
Glenda
G
Canderan
Abdelali
A
Filali-Mouhim
Tedi E
TE
Asher
David R
DR
Ambrozak
Phillip
P
Scheinberg
Mohamad Rachid
MR
Boulassel
Jean-Pierre
JP
Routy
Richard A
RA
Koup
Daniel C
DC
Douek
Rafick-Pierre
RP
Sekaly
Lydie
L
Trautmann
D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D002999:Clone Cells; D005786:Gene Expression Regulation / Q000276:immunology; D006678:HIV / Q000276:immunology*; D006801:Humans; D053699:Interleukin-7 Receptor alpha Subunit; D017493:Leukocyte Common Antigens; D008137:Longitudinal Studies; D061026:Programmed Cell Death 1 Receptor
D000956:Antigens, Viral; D053699:Interleukin-7 Receptor alpha Subunit; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D017493:Leukocyte Common Antigens