A New Unconventional HLA-A2-restricted Epitope from HBV Core Protein Elicits Antiviral Cytotoxic T Lymphocytes

Overview

Journal Protein Cell

Publisher Oxford University Press

Specialties Biochemistry
Cell Biology

Date 2014 Mar 25

PMID 24659387

Citations 12

Authors

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

Affiliations

Soon will be listed here.

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.

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