title: Identification of new immunogenic peptides in conserved regions of hepatitis C virus (HCV) 1b with the potentiality to generate cytotoxic T lymphocytes in HCV1b(+) HLA-A24(+) patients.
abstract: OBJECTIVE
  Hepatitis C virus (HCV) 1b is resistant to standard interferon therapy and has a high risk of developing into hepatocellular carcinoma at the late stage of infection. Therefore, new therapeutic modalities for HCV1b infection must be developed. One approach would be active specific immunotherapy with highly immunogenic HCV1b peptides.
  
  
  METHODS
  HCV1b-derived 44 synthetic peptides were selected based on their binding scores to HLA-A24. Peptide-specific IgG were measured by ELISA. Peptide-specific cytotoxic T-lymphocytes (CTLs) were induced in vitro by repeated peptide-stimulation.
  
  
  RESULTS
  We identified three novel candidate peptides of HCV1b proteins containing HLA-A24 binding motifs. Each of them had the ability to induce HLA-A24-restricted and peptide-specific CTL activity, and IgGs specific to each of them were detected in the plasma of HCV1b patients. Among these three peptides, a peptide NS5A 2132-2142 was recognized by both cellular and humoral immunities in the majority of blood samples of patients tested. More importantly, the peptide-stimulated peripheral blood mononuclear cells (PBMCs) showed cytotoxicity against cells cotransfected with NS5A and HLA-A2402 genes in an HLA-restricted manner. This is an additional report to our previous study.
  
  
  CONCLUSIONS
  These findings may provide a new insight into the development of a peptide-based specific immunotherapy for HCV1b-infected patients.
authors.affiliation: Department of Immunology, Kurume University, Kurume, Fukuoka, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Takao
authors.forename: Akira
authors.initials: A
authors.lastname: Yamada
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yutani
authors.forename: Hiroko
authors.initials: H
authors.lastname: Takedatsu
authors.forename: Takeharu
authors.initials: T
authors.lastname: Ono
authors.forename: Kojyu
authors.initials: K
authors.lastname: Etoh
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Susumu
authors.initials: S
authors.lastname: Suzuki
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ide
authors.forename: Kunitada
authors.initials: K
authors.lastname: Shimotohno
authors.forename: Michio
authors.initials: M
authors.lastname: Sata
authors.forename: Kyogo
authors.initials: K
authors.lastname: Itoh