Transduction of human T cells with a novel T-cell receptor confers anti-HCV reactivity

Hepatitis c virus (hcv) is a major public health concern,with no effective vaccines currently available and 3% of the world's population being infected. despite the existence of both b- and t-cell immunity in hcv-infected patients,chronic viral infection and hcv-related malignancies progress. here we report the identification of a novel hcv tcr from an hla-a2-restricted,hcv ns3:1073-1081-reactive ctl clone isolated from a patient with chronic hcv infection. we characterized this hcv tcr by expressing it in human t cells and analyzed the function of the resulting hcv tcr-transduced cells. our results indicate that both the hcv tcr-transduced cd4+ and cd8+ t cells recognized the hcv ns3:1073-1081 peptide-loaded targets and hcv+ hepatocellular carcinoma cells (hcc) in a polyfunctional manner with cytokine (ifn-c,il-2,and tnf-a) production as well as cytotoxicity. tumor cell recognition by hcv tcr transduced cd82 jurkat cells and cd4+ pbl-derived t cells indicated this tcr was cd8-independent,a property consistent with other high affinity tcrs. hcv tcr-transduced t cells may be promising for the treatment of patients with chronic hcv infections. © 2010 zhang et al.