Identification of hepatitis B virus-specific CTL epitopes presented by HLA-A*2402, the most common HLA class I allele in East Asia.
OBJECTIVE
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.
Sobao
Y
Y
Division of Viral Immunology, Center for AIDS Research, Kumamoto University, Japan.
Sugi
K
K
Tomiyama
H
H
Saito
S
S
Fujiyama
S
S
Morimoto
M
M
Hasuike
S
S
Tsubouchi
H
H
Tanaka
K
K
Takiguch
M
M
D000208:Acute Disease; D000483:Alleles; D017951:Antigen Presentation; D002999:Clone Cells; D005202:Asia, Eastern; D015234:HLA-A Antigens / Q000235:genetics / Q000378:metabolism*; D059871:HLA-A24 Antigen; D006509:Hepatitis B / Q000235:genetics / Q000276:immunology* / Q000821:virology; D006511:Hepatitis B Antigens / Q000378:metabolism*; D019694:Hepatitis B, Chronic / Q000235:genetics / Q000276:immunology / Q000821:virology; D006801:Humans; D016056:Immunodominant Epitopes / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D006511:Hepatitis B Antigens; D016056:Immunodominant Epitopes