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Journal of Virology, March 2008, p. 3147-3153, Vol. 82, No. 6
0022-538X/08/$08.00+0     doi:10.1128/JVI.02252-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Increased Cytotoxic T-Lymphocyte Epitope Variant Cross-Recognition and Functional Avidity Are Associated with Hepatitis C Virus Clearance{triangledown}

Daniel Yerly,1,2 David Heckerman,3 Todd M. Allen,2 John V. Chisholm III,2 Kellie Faircloth,2 Caitlyn H. Linde,2 Nicole Frahm,2 Joerg Timm,4 Werner J. Pichler,1 Andreas Cerny,5 and Christian Brander2*

University of Bern, Clinic for Rheumatology and Clinical Immunology/Allergology, CH-3010 Bern, Switzerland,1 Massachusetts General Hospital and Harvard Medical School, Partners AIDS Research Center, Boston, Massachusetts,2 Microsoft Research, Redmond, Washington 98052,3 University Hospital Essen, Institute for Virology, Essen, Germany,4 Ospedale Regionale di Lugano, Department of Medicine, CH-6903 Lugano, Switzerland5

Received 17 October 2007/ Accepted 27 December 2007

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.

* Corresponding author. Mailing address: Massachusetts General Hospital and Harvard Medical School, Partners AIDS Research Center, MGH East no. 5239, 149 13th St., Charlestown, MA 02143. Phone: (617) 724-5789. Fax: (617) 726-5345. E-mail: cbrander{at}partners.org

{triangledown} Published ahead of print on 9 January 2008.

Journal of Virology, March 2008, p. 3147-3153, Vol. 82, No. 6
0022-538X/08/$08.00+0     doi:10.1128/JVI.02252-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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