Journal
PROTEIN & CELL
Volume 5, Issue 4, Pages 317-327Publisher
SPRINGEROPEN
DOI: 10.1007/s13238-014-0041-4
Keywords
chronic hepatitis B; HLA-A2; HBc peptide; CTL response; antiviral cytotoxity
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Funding
- National Basic Research Program (973 Program) [2014CB542602]
- National Natural Science Foundation of China [31230026, 91029724, 81021003, 81102018]
- Key Projects in the National Science and Technology Program [2013ZX10002001]
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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.
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