Selective expansion of high functional avidity memory CD8 T cell clonotypes during hepatitis C virus reinfection and clearance.
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.
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.
Mohamed S
MS
Abdel-Hakeem
Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Québec, Canada.
Maude
0000-0001-9304-7796
M
Boisvert
Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Québec, Canada.|Département de médecine familiale et de médecine d'urgence, Université de Montréal, Montréal, Québec, Canada.
Julie
J
Bruneau
Département de microbiologie, infectiologie et immunologie, Université de Montréal, Montréal, Québec, Canada.|Centre hospitalier universitaire Sainte-Justine, Montréal, Québec, Canada.
Hugo
0000-0001-5857-3176
H
Soudeyns
Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Québec, Canada.|Département de médecine, Université de Montréal, Montréal, Québec, Canada.
Naglaa H
0000-0002-8817-8238
NH
Shoukry
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005434:Flow Cytometry; D016174:Hepacivirus / Q000276:immunology; D006526:Hepatitis C / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta