The high prevalence of the I27 mutant HBcAg18-27 epitope in Chinese HBV-infected patients and its cross-reactivity with the V27 prototype epitope.
HBcAg18-27 (FLPSDFFPSV, V27 epitope) is a dominant HLA-A2-restricted epitope in hepatitis B virus (HBV)-infected patients. So far, the occurrence of the epitope has not been assessed in China, where the prevalence of chronic HBV infection is high. In this report, we sequenced the HBV core gene in 105 Chinese patients with chronic HBV infection. Approximately 93.3% (98/105) of the core genes that were sequenced contained mutations with amino acid substitution at position 27 of the core protein: a mutation from a valine to an isoleucine (V27I). The mutant peptide (FLPSDFFPSI, I27) was found to bind to the HLA-A2 molecule with high affinity and elicit specific cytotoxic T lymphocyte (CTL) responses in acutely infected hepatitis B patients. In CTL assays using I27-specific pentamer staining, the V27 epitope showed a cross-reactive T cell response specific for the I27 epitope, but not vice versa. These findings provide important insights for the design of HBcAg18-27-based vaccines in the future.
Liu
Heng-Gui
HG
Center for Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080, China.
Chen
Wei-wei
WW
Fan
Zhen-Ping
ZP
Yang
Hui-ying
HY
Shi
Ming
M
Zhang
Zheng
Z
Luan
Shen-Shun
SS
Zhang
Hui
H
Lu
Peng
P
Tien
Po
P
Wang
Fu-Sheng
FS
D000595:Amino Acid Sequence; D002681:China; D003429:Cross Reactions; D018984:Epitopes, T-Lymphocyte / Q000235:genetics* / Q000276:immunology; D005434:Flow Cytometry; D015789:HLA-A2 Antigen / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D006512:Hepatitis B Core Antigens / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D015995:Prevalence; D017433:Protein Structure, Secondary; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D006512:Hepatitis B Core Antigens