title: Increased cytotoxic T-lymphocyte epitope variant cross-recognition and functional avidity are associated with hepatitis C virus clearance.
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.
authors.affiliation: Massachusetts General Hospital and Harvard Medical School, Partners AIDS Research Center, MGH East no. 5239, 149 13th St., Charlestown, MA 02143, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Yerly
authors.forename: David
authors.initials: D
authors.lastname: Heckerman
authors.forename: Todd M
authors.initials: TM
authors.lastname: Allen
authors.forename: John V
authors.initials: JV
authors.lastname: Chisholm
authors.forename: Kellie
authors.initials: K
authors.lastname: Faircloth
authors.forename: Caitlyn H
authors.initials: CH
authors.lastname: Linde
authors.forename: Nicole
authors.initials: N
authors.lastname: Frahm
authors.forename: Joerg
authors.initials: J
authors.lastname: Timm
authors.forename: Werner J
authors.initials: WJ
authors.lastname: Pichler
authors.forename: Andreas
authors.initials: A
authors.lastname: Cerny
authors.forename: Christian
authors.initials: C
authors.lastname: Brander
mesh_terms: D000595:Amino Acid Sequence; D000915:Antibody Affinity; D000939:Epitopes / Q000276:immunology*; D016174:Hepacivirus / Q000276:immunology / Q000502:physiology*; D006526:Hepatitis C / Q000276:immunology* / Q000821:virology; D006801:Humans; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000939:Epitopes