A new unconventional HLA-A2-restricted epitope from HBV core protein elicits antiviral cytotoxic T lymphocytes.
- Author:
Lu SUN
;
Yu ZHANG
;
Bao ZHAO
;
Mengmeng DENG
;
Jun LIU
;
Xin LI
;
Junwei HOU
;
Mingming GUI
;
Shuijun ZHANG
;
Xiaodong LI
;
George F GAO
;
Songdong MENG
- Publication Type:Journal Article
- MeSH:
Adult;
Amino Acid Sequence;
Animals;
Binding Sites;
Epitopes;
chemistry;
immunology;
metabolism;
Female;
Genotype;
HEK293 Cells;
HLA-A2 Antigen;
metabolism;
Hepatitis B Core Antigens;
chemistry;
immunology;
metabolism;
Hepatitis B virus;
genetics;
metabolism;
Humans;
Hydrogen Bonding;
Male;
Mice;
Mice, Inbred BALB C;
Mice, Transgenic;
Middle Aged;
Molecular Dynamics Simulation;
Mutation;
Protein Binding;
Protein Structure, Tertiary;
T-Lymphocytes, Cytotoxic;
immunology;
metabolism
- From:
Protein & Cell
2014;5(4):317-327
- CountryChina
- Language:English
-
Abstract:
Cytotoxic T cells (CTLs) play a key role in the control of Hepatitis B virus (HBV) infection and viral clearance. However, most of identified CTL epitopes are derived from HBV of genotypes A and D, and few have been defined in virus of genotypes B and C which are more prevalent in Asia. As HBV core protein (HBc) is the most conservative and immunogenic component, in this study we used an overlapping 9-mer peptide pool covering HBc to screen and identify specific CTL epitopes. An unconventional HLA-A2-restricted epitope HBc141-149 was discovered and structurally characterized by crystallization analysis. The immunogenicity and anti-HBV activity were further determined in HBV and HLA-A2 transgenic mice. Finally, we show that mutations in HBc141-149 epitope are associated with viral parameters and disease progression in HBV infected patients. Our data therefore provide insights into the structure characteristics of this unconventional epitope binding to MHC-I molecules, as well as epitope specific CTL activity that orchestrate T cell response and immune evasion in HBV infected patients.
