Molecular Mimicry of Human Cytochrome P450 by Hepatitis C Virus at the Level of Cytotoxic T Cell Recognition

Kammer, Andreas R.; van der Burg, Sjoerd H.; Grabscheid, Benno; Hunziker, Isabelle P.; Kwappenberg, Kitty M.C.; Reichen, Jürg; Melief, Cornelis J.M.; Cerny, Andreas

Stability. To characterize the HLA-A2 binding properties of HCV core 178 and the homologous CYP peptides, we determined their affinity to HLA-A2 and the stability of the formed HLA-A2-peptide complexes. The HCV core 178 bound to HLA-A2 with intermediate affinity as previously described (28) , whereas both CYP peptides bound with low affinity (Fig. 1 A) . Similar results were obtained measuring the peptide-induced stabilization of HLA-A2 molecules at the surface of transporter-associated with antigen processing-deficient T2 cells (data not shown). Determination of MHC-peptide complex stability showed that the HCV core 178 peptide was able to form stable complexes with a half-life of ‫5ف‬ h. The CYP2A6 8-17 as well as the CYP2A7 8-17 peptides dissociated much faster with half-lives of ‫1ف‬ h (Fig. 1 B) .