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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.

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


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.

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