title: A new unconventional HLA-A2-restricted epitope from HBV core protein elicits antiviral cytotoxic T lymphocytes.
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.
authors.forename: Lu
authors.initials: L
authors.lastname: Sun
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Bao
authors.initials: B
authors.lastname: Zhao
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Deng
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Junwei
authors.initials: J
authors.lastname: Hou
authors.forename: Mingming
authors.initials: M
authors.lastname: Gui
authors.forename: Shuijun
authors.initials: S
authors.lastname: Zhang
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Li
authors.forename: George F
authors.initials: GF
authors.lastname: Gao
authors.forename: Songdong
authors.initials: S
authors.lastname: Meng
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D000939:Epitopes / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005838:Genotype; D057809:HEK293 Cells; D015789:HLA-A2 Antigen / Q000378:metabolism*; D006512:Hepatitis B Core Antigens / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006860:Hydrogen Bonding; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008875:Middle Aged; D056004:Molecular Dynamics Simulation; D009154:Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism
chemical_list: D000939:Epitopes; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D006512:Hepatitis B Core Antigens