Silvia Giugliano
Master of Biological Sciences (M.Sc.), Third University of Rome, 2006
Impact of HCV sequence variability on immune control
The goal of this study is to compare genotype-specific cellular immune response against HCV in a cohort of injection drug users. Patients who are positive for HCV antibodies (marker for exposure to HCV) are recruited at the Department for Addictive Behaviour and Addiction Medicine, Rhine State Hospital Essen. The majority of these patients are infected with genotype 3 and about 30% of the patients are infected with genotype 1. 20% of the recruited patients have undetectable HCV-RNA and were seemingly able to resolve an HCV infection. T cell epitopes are identified with overlapping peptides spanning the NS3 protein of genotype 1 and 3. This region is amplified from the viral RNA and sequenced, in order to identify differences between the synthetic peptides used and the autologous sequence. The degree of genotype cross-reactivity between the immunodominant epitopes is characterized in-vitro using serial dilutions after the expansion of specific T cell lines. In the first pilot experiments there is evidence that the majority of the identified T cell responses are directed against a historical antigen. In case of matching between the autologous viral sequence and the detected targeted epitope sequence, alternative mechanisms for T cell failure will be explored. It will therefore be tested if the phenotype and functionality of specific T cells differ between these two groups. The expression levels of different differentiation markers and the functional profile of effector cells will be determined by FACS analysis.
1st supervisor: PD Dr. Jörg Timm Institute: Telephone: +49 (0)201 - 723 - 2875 |