Analysis of the hepatitis C virus specific CD4+ T cell response in different phases of chronic hepatitis C using novel HLA class II tetramers.

• Applicant: Dr. Axel Ulsenheimer
• Subject Area: Gastroenterology
• Term: from 2008 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 74811176

Hepatitis C virus (HCV) infection is one of the most common chronic viral diseases worldwide and a leading cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma. Acute HCV infection progresses to chronic hepatitis C in up to 85% of cases yet no preventive vaccine is available. Of those chronically infected, only about 50% can be cured by currently available therapies, which are expensive and not easily tolerated. HCV-specific immunotherapies may represent new strategies to both treat chronic hepatitis C and/or to induce protective immunity. However, their development depends on a detailed definition of HCV specific immune responses and the immunopathogenesis of chronic viral persistence. Observations both in humans and in animal models suggest that a failure of HCV specific CD4+ T cell responses is critical in the pathogenesis of chronic viral persistence and a better understanding of the underlying molecular mechanisms may hold the key to overcome HCV persistence. In this grant proposal, we intend to use recently developed HCV-specific HLA class II tetramers to study the evolution of HCV specific CD4+ T cell responses in critical phases of acute and chronic hepatitis C. The tetramer technology will allow a precise enumeration and phenotyping of HCV specific CD4+ T cells. In combination with functional assays this will help to identify the underlying mechanisms associated with T cell failure in patients with chronic hepatitis C. In the second part of the study, the tetramer technology will be used to develop and monitor strategies to restore HCV-specific CD4+ T cell responses in-vitro. These in vitro experiments can subsequently guide the development of immunotherapeutic strategies to treat patients with chronic hepatitis C.

• DFG Programme: Research Grants
• Participating Person: Professor Dr. Helmut Diepolder