A mutant HBs antigen (HBsAg)183-191 epitope elicits specific cytotoxic T lymphocytes in acute hepatitis B patients.
HBs antigen (HBsAg)183-191 (FLLTRILTI, R187 peptide) is a dominant human leucocyte antigen-A2 (HLA-A2)-restricted epitope associated with hepatitis B virus (HBV) infection in Caucasian populations. However, its prevalence is poorly understood in China, where there is a high incidence of HBV infection. In this report, we sequenced the region of HBsAg derived from 103 Chinese patients. Approximately 16.5% of the patients bore a mutant HBsAg183-191 epitope in which the original arginine (R187) was substituted with a lysine (K187 mutant peptide). Importantly, K187 still bound to HLA-A2 with high affinity, and elicited specific cytotoxic T lymphocyte (CTL) responses in HLA-A2/K(b) transgenic mice. K187-specific CTLs were also generated successfully in acute hepatitis B (AHB) patients, indicating that this mutant epitope is processed and presented effectively. Our findings show that R187-specific CTLs can cross-react with the K187 peptide. These findings reveal that K187 still has the property of an HLA-A2 restricted epitope, and elicits a protective anti-HBV CTL response in humans.
Liu
H-G
HG
Center for Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, and Graduate University of Chinese Academy of Sciences, Beijing, China.
Fan
Z-P
ZP
Chen
W-W
WW
Yang
H-Y
HY
Liu
Q-F
QF
Zhang
H
H
Tien
P
P
Wang
F-S
FS
D000208:Acute Disease; D000818:Animals; D017951:Antigen Presentation; D003429:Cross Reactions / Q000276:immunology; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D015789:HLA-A2 Antigen / Q000378:metabolism; D006509:Hepatitis B / Q000235:genetics* / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000235:genetics* / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D017510:Protein Folding; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000939:Epitopes; D015789:HLA-A2 Antigen; D006514:Hepatitis B Surface Antigens