IL28B genotype and hepatitis C virus specific T cell response

Single nucleotide polymorphisms (SNP) in the IL28B gene region on chromosome 19 are important in predicting natural course and therapy outcome in chronic hepatitis C virus (HCV) infection. This finding might be of major importance in clinical treatment decision-making in the near future. Until now, the mechanisms behind this observation are unknown. We could show previously that CD8+ T cells play a pivotal role in HCV pathogenesis and viral clearance. Therefore, we asked whether the IL28B genotype is mechanistically linked to HCV-specific CD8+ T cell responses. We analyzed CD8+ T cell responses in a well-characterized cohort (n=20) of HCV patients using overlapping peptides in a matrix set-up Elispot assay and confirmed positive responses by intracellular IFN-γ staining using individual peptides. In addition, we determined the SNP rs12979860 genotype. We could show that for SNP rs12979860, there are no significant differences in the number of epitopes recognized by HCV-specific T cells or the T cell frequency of individuals with the favorable genotype C/C compared to genotypes C/T or T/T. Importantly, this holds true for the intrahepatic compartment as well as for peripheral blood. In agreements with previous findings we could show that in the majority of patients with the favorable genotype C/C antiviral therapy with pegylated IFN was successful. This finding suggests that there is no mechanistic link between the rs12979860 genotype and the adaptive HCV-specific CD8+ T cell response.

CD8+ T cell - HCV - IL28B - SNP - immunology