title: Transduction of human T cells with a novel T-cell receptor confers anti-HCV reactivity.
abstract: 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.
authors.affiliation: Division of Transplantation, Department of Surgery, Medical University of South Carolina, Hollings Cancer Center, Charleston, South Carolina, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yeuying
authors.initials: Y
authors.lastname: Liu
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Moxley
authors.forename: Lucy
authors.initials: L
authors.lastname: Golden-Mason
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hughes
authors.forename: Tongxin
authors.initials: T
authors.lastname: Liu
authors.forename: Mirjam H M
authors.initials: MH
authors.lastname: Heemskerk
authors.forename: Hugo R
authors.initials: HR
authors.lastname: Rosen
authors.forename: Michael I
authors.initials: MI
authors.lastname: Nishimura
mesh_terms: D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D016174:Hepacivirus / Q000276:immunology*; D006505:Hepatitis / Q000628:therapy; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D019169:Jurkat Cells; D009369:Neoplasms / Q000628:therapy; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*; D014161:Transduction, Genetic; D017361:Viral Nonstructural Proteins / Q000276:immunology; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000951:Antigens, Neoplasm; D011948:Receptors, Antigen, T-Cell; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases