BACKGROUND/AIMS: The aim of this study was to identify and characterize hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTL) epitopes presented by human leukocyte antigen (HLA)-A*2402, most common HLA class I allele in East Asia. METHODS: HLA-A*2402-restricted CTL epitopes were identified by reverse immunogenetics. Immunogenecity of these epitopes was investigated using peripheral blood mononuclear cell (PBMC) from HLA-A24+ patients with acute hepatitis B. RESULTS: An HLA-A*2402 stabilization assay demonstrated that 36 of 63 HBV peptides carrying HLA-A*2402 anchor residues have high- and medium-HLA-A*2402 binding affinity. Two (C117-125 and P756-764) of the 36 peptides induced peptide-specific CTLs. CTL clones and lines specific for these peptides killed HBV recombinant vaccinia virus-infected target cells expressing HLA-A*2402, indicating that these two peptides are CTL epitopes presented by HLA-A*2402. These two peptides were able to induce specific CTLs in 7 and 11 of 12 HLA-A24+ patients with acute hepatitis B, respectively. CONCLUSIONS: We identified two immunodominant CTL epitopes restricted by HLA-A*2402. Because HLA-A*2402 is the most common allele in East Asia, a region in which there are approximately 200 million HBV carriers, these epitopes will be useful for analysis of CTL responses in patients from East Asia.
BACKGROUND/AIMS: The aim of this study was to identify and characterize hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTL) epitopes presented by human leukocyte antigen (HLA)-A*2402, most common HLA class I allele in East Asia. METHODS: HLA-A*2402-restricted CTL epitopes were identified by reverse immunogenetics. Immunogenecity of these epitopes was investigated using peripheral blood mononuclear cell (PBMC) from HLA-A24+ patients with acute hepatitis B. RESULTS: An HLA-A*2402 stabilization assay demonstrated that 36 of 63 HBV peptides carrying HLA-A*2402 anchor residues have high- and medium-HLA-A*2402 binding affinity. Two (C117-125 and P756-764) of the 36 peptides induced peptide-specific CTLs. CTL clones and lines specific for these peptides killed HBV recombinant vaccinia virus-infected target cells expressing HLA-A*2402, indicating that these two peptides are CTL epitopes presented by HLA-A*2402. These two peptides were able to induce specific CTLs in 7 and 11 of 12 HLA-A24+ patients with acute hepatitis B, respectively. CONCLUSIONS: We identified two immunodominant CTL epitopes restricted by HLA-A*2402. Because HLA-A*2402 is the most common allele in East Asia, a region in which there are approximately 200 million HBV carriers, these epitopes will be useful for analysis of CTL responses in patients from East Asia.
Authors: Christopher P Desmond; Silvana Gaudieri; Ian R James; Katja Pfafferott; Abha Chopra; George K Lau; Jennifer Audsley; Caroline Day; Sarah Chivers; Adam Gordon; Peter A Revill; Scott Bowden; Anna Ayres; Paul V Desmond; Alexander J Thompson; Stuart K Roberts; Stephen A Locarnini; Simon A Mallal; Sharon R Lewin Journal: J Virol Date: 2011-11-09 Impact factor: 5.103
Authors: K Kobayashi; M Ishii; M Shiina; Y Ueno; Y Kondo; A Kanno; Y Miyazaki; T Yamamoto; T Kobayashi; H Niitsuma; Y Kikumoto; H Takizawa; T Shimosegawa Journal: Clin Exp Immunol Date: 2005-07 Impact factor: 4.330
Authors: William G H Abbott; Peter Tsai; Euphemia Leung; Alex Trevarton; Malakai Ofanoa; John Hornell; Edward J Gane; Stephen R Munn; Allen G Rodrigo Journal: J Virol Date: 2010-01 Impact factor: 5.103
Authors: Anthony Tanoto Tan; Elisabetta Loggi; Carolina Boni; Adeline Chia; Adam J Gehring; Konduru S R Sastry; Vera Goh; Paola Fisicaro; Pietro Andreone; Christian Brander; Seng Gee Lim; Carlo Ferrari; Florian Bihl; Antonio Bertoletti Journal: J Virol Date: 2008-09-17 Impact factor: 5.103