Increased Cytotoxic T-Lymphocyte Epitope Variant Cross-Recognition and Functional Avidity Are Associated with Hepatitis C Virus Clearance
- Daniel Yerly ,
- David Heckerman ,
- Todd M. Allen ,
- John V. Chisholm III ,
- Kellie Faircloth ,
- Caitlyn H. Linde ,
- Nicole Frahm ,
- Joerg Timm ,
- Werner J. Pichler ,
- Andreas Cerny ,
- Christian Brander
Journal of Virology | , Vol 82(6): pp. 3147-3153
Hepatitis C virus (HCV) clearance has been associated with reduced viral evolution in targeted cytotoxic T-lymphocyte (CTL) epitopes, suggesting that HCV clearers may mount CTL responses with a superior ability to recognize epitope variants and prevent viral immune escape. Here, 40 HCV-infected subjects were tested with 406 10-mer peptides covering the vast majority of the sequence diversity spanning a 197-residue region of the NS3 protein. HCV clearers mounted significantly broader CTL responses of higher functional avidity and with wider variant cross-recognition capacity than nonclearers. These observations have important implications for vaccine approaches that may need to induce high-avidity responses in vivo.