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PLoS Pathog. 2017 Feb 1;13(2):e1006191. doi: 10.1371/journal.ppat.1006191. eCollection 2017 Feb.

Selective expansion of high functional avidity memory CD8 T cell clonotypes during hepatitis C virus reinfection and clearance.

Author information

1
Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Québec, Canada.
2
Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
3
Département de microbiologie, infectiologie et immunologie, Université de Montréal, Montréal, Québec, Canada.
4
Département de médecine familiale et de médecine d'urgence, Université de Montréal, Montréal, Québec, Canada.
5
Centre hospitalier universitaire Sainte-Justine, Montréal, Québec, Canada.
6
Département de médecine, Université de Montréal, Montréal, Québec, Canada.

Abstract

The dynamics of the memory CD8 T cell receptor (TCR) repertoire upon virus re-exposure and factors governing the selection of TCR clonotypes conferring protective immunity in real life settings are poorly understood. Here, we examined the dynamics and functionality of the virus-specific memory CD8 TCR repertoire before, during and after hepatitis C virus (HCV) reinfection in patients who spontaneously resolved two consecutive infections (SR/SR) and patients who resolved a primary but failed to clear a subsequent infection (SR/CI). The TCR repertoire was narrower prior to reinfection in the SR/SR group as compared to the SR/CI group and became more focused upon reinfection. CD8 T cell clonotypes expanding upon re-exposure and associated with protection from viral persistence were recruited from the memory T cell pool. Individual CD8 T cell lines generated from the SR/SR group exhibited higher functional avidity and polyfunctionality as compared to cell lines from the SR/CI group. Our results suggest that protection from viral persistence upon HCV reinfection is associated with focusing of the HCV-specific CD8 memory T cell repertoire from which established cell lines showed high functional avidity. These findings are applicable to vaccination strategies aiming at shaping the protective human T cell repertoire.

PMID:
28146579
PMCID:
PMC5305272
DOI:
10.1371/journal.ppat.1006191
[Indexed for MEDLINE]
Free PMC Article

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