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

PLoS Pathog. 2010 Jul 29;6(7):e1001018. doi: 10.1371/journal.ppat.1001018.


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-gamma, IL-2, and TNF-alpha) production as well as cytotoxicity. Tumor cell recognition by HCV TCR transduced CD8(-) 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antigen Presentation
  • Antigens, Neoplasm / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line, Tumor
  • Cells, Cultured
  • Hepacivirus / immunology*
  • Hepatitis / therapy
  • Humans
  • Immunotherapy / methods*
  • Jurkat Cells
  • Neoplasms / therapy
  • Receptors, Antigen, T-Cell / genetics*
  • T-Lymphocytes / immunology*
  • Transduction, Genetic*
  • Viral Nonstructural Proteins / immunology


  • Antigens, Neoplasm
  • NS3 protein, hepatitis C virus
  • Receptors, Antigen, T-Cell
  • Viral Nonstructural Proteins