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-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.
Zhang
Yi
Y
Division of Transplantation, Department of Surgery, Medical University of South Carolina, Hollings Cancer Center, Charleston, South Carolina, USA.
Liu
Yeuying
Y
Moxley
Kelly M
KM
Golden-Mason
Lucy
L
Hughes
Michael G
MG
Liu
Tongxin
T
Heemskerk
Mirjam H M
MH
Rosen
Hugo R
HR
Nishimura
Michael I
MI
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
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