1. Identification of hepatitis B virus-specific CTL epitopes presented by HLA-A*2402, the most common HLA class I allele in East Asia.
- Author
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Sobao Y, Sugi K, Tomiyama H, Saito S, Fujiyama S, Morimoto M, Hasuike S, Tsubouchi H, Tanaka K, and Takiguch M
- Subjects
- Acute Disease, Alleles, Antigen Presentation, Clone Cells, Asia, Eastern, HLA-A Antigens genetics, HLA-A24 Antigen, Hepatitis B genetics, Hepatitis B virology, Hepatitis B, Chronic genetics, Hepatitis B, Chronic immunology, Hepatitis B, Chronic virology, Humans, Immunodominant Epitopes metabolism, Leukocytes, Mononuclear immunology, HLA-A Antigens metabolism, Hepatitis B immunology, Hepatitis B Antigens metabolism, T-Lymphocytes, Cytotoxic immunology
- Abstract
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.
- Published
- 2001
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