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Journal of Virology
Year: 2008  |  Volume: 82  |  Issue: 6  |  Page No.: 3147 - 3153

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 and Christian Brander    

Abstract: 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.

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