Regulation und Modulation der unspezifischen und spezifischen Immunität in der murinen Leber durch das Hepatitis C Virus core Protein

• Applicant: Dr. Mona Wegert, since 12/2009
• Subject Area: Immunology
• Term: from 2004 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5432998

The 191-residue hepatitis C core (HCVc) protein of the hepatitis C virus (HCV) is a T cell antigen. It activates signaling pathways within the cell that might be important for its antigenic properties. The first part of the project will examine HCVc-triggered signals that activate NK-kB/Rel, or interferon (IFN)/JAK/STAT pathways. Their role in promoting processing, presenting and/or costimulating in the priming of HCV-specific CD8+ T cell responses (through effects on dendritic cells or the innate immune system) will be investigated. Attempts will be made to distinguish and separate signaling HCVc motifs that either enhande, or down modulate HCVc immunogenicity. It successful, motifs that enhance the immunogenicity of HCVc for CD8+ T cells will be incorprated into DNA- or peptide-based vaccines. In the second part of the project, anti-HCVc-specific CD8+ T cell responses restricted by murine or human MHC class I molecules will be primed in normal (B6, BALB/c) or A2-tg (HHB) mice. Novel peptide- and DNA-based vaccination approaches (developed in the group) will be used to map new epitopes and to define immunogenic formulations. The goal of the project is the design of an optimized HCVc immunogen delivering immune-enhancing signals (but with deleted immunosuppressive signals) that efficiently primes A2-restricted T cell responses. This HCVs immunogen could be a component of the vaccine against HCV.

• DFG Programme: Research Grants
• Ehemaliger Antragsteller: Privatdozent Dr. Nektarios Dikopoulos, from 6/2008 until 12/2009