Protection from persistent hepatitis C virus infection by HLA class I: The need for multiple escape mutations in immunodominant T cell epitopes is a common feature

Certain HLA class I alleles are associated with spontaneous resolution of acute hepatitis C virus (HCV) infection. We have recently elucidated the mechanisms of protection by HLA-B27. Viral escape from an immunodominant (Dazert, Neumann-Haefelin et al., J Clin Invest 2009) as well as from a subdominant HLA-B27 restricted HCV-specific CD8+ T cell response (Neumann-Haefelin et al., manuscript submitted) requires the emergence of multiple mutations within a single viral genome, suggesting escape from HLA-B27 restricted CD8+ T cell responses can not occur easily. This may lead to viral clearance rather than viral ev…