Increased cytotoxic T-lymphocyte epitope variant cross-recognition and functional avidity are associated with hepatitis C virus clearance.
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.
Yerly
Daniel
D
Massachusetts General Hospital and Harvard Medical School, Partners AIDS Research Center, MGH East no. 5239, 149 13th St., Charlestown, MA 02143, USA.
Heckerman
David
D
Allen
Todd M
TM
Chisholm
John V
JV
Faircloth
Kellie
K
Linde
Caitlyn H
CH
Frahm
Nicole
N
Timm
Joerg
J
Pichler
Werner J
WJ
Cerny
Andreas
A
Brander
Christian
C
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*
D000939:Epitopes