Selective expansion of high functional avidity memory CD8 T cell clonotypes during hepatitis C virus reinfection and clearance
نویسندگان
چکیده
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.
منابع مشابه
Kinetic analysis by real-time PCR of hepatitis C virus (HCV)-specific T cells in peripheral blood and liver after challenge with HCV.
Intrahepatic virus-specific CD8(+) T cells are thought to be important for the control of hepatitis C virus (HCV) infection, yet the precise kinetics for the expansion of epitope-specific T cells over the course of infection are difficult to determine with currently available methods. We used a real-time PCR assay to measure the frequency of clonotypic HCV-specific CD8(+) T cells in peripheral ...
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