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. © 2017 abdel-hakeem et al.