Increased cytotoxic T-lymphocyte epitope variant cross-recognition and functional avidity are associated with hepatitis C virus clearance |
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Authors: | Yerly Daniel Heckerman David Allen Todd M Chisholm John V Faircloth Kellie Linde Caitlyn H Frahm Nicole Timm Joerg Pichler Werner J Cerny Andreas Brander Christian |
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Affiliation: | Massachusetts General Hospital and Harvard Medical School, Partners AIDS Research Center, MGH East no. 5239, 149 13th St., Charlestown, MA 02143, USA. |
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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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