Increased CTL epitope variant cross-recognition and functional avidity are associated with HCV clearance

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

	Abstract

Hepatitis C Virus (HCV) clearance has been associated with reduced viral evolution in targeted 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 10mer peptides covering the vast majority of the sequence diversity spanning a 197 residues region of the NS3 protein. HCV clearers mounted significantly broader CTL responses of higher functional avidity and with wider variant cross-recognition capacity than non-clearers. These observations have important implications for vaccine approaches that may need to induce high avidity responses in-vivo.