Please use this identifier to cite or link to this item: https://doi.org/10.1128/JVI.01457-18
Title: Spatiotemporal Differences in Presentation of CD8 T Cell Epitopes during Hepatitis B Virus Infection
Authors: Khakpoor, Atefeh 
Ni, Yi
Chen, Antony 
Ho, Zi Zong 
Oei, Vincent
Yang, Ninghan
Giri, Reshmi 
Chow, Jia Xin 
Tan, Anthony T 
Kennedy, Patrick T
Maini, Mala
Urban, Stephan
Bertoletti, Antonio 
Keywords: Science & Technology
Life Sciences & Biomedicine
Virology
antigen presentation
CD8(+) T cells
chronic hepatitis B patient
HBV DNA integration
HLA class I
liver
hepatitis B virus
VIRAL-ANTIGEN
HBV
EXPRESSION
IMMUNODOMINANCE
PATHOGENESIS
HBSAG
CORE
Issue Date: 1-Feb-2019
Publisher: AMERICAN SOCIETY FOR MICROBIOLOGY
Citation: Khakpoor, Atefeh, Ni, Yi, Chen, Antony, Ho, Zi Zong, Oei, Vincent, Yang, Ninghan, Giri, Reshmi, Chow, Jia Xin, Tan, Anthony T, Kennedy, Patrick T, Maini, Mala, Urban, Stephan, Bertoletti, Antonio (2019-02-01). Spatiotemporal Differences in Presentation of CD8 T Cell Epitopes during Hepatitis B Virus Infection. JOURNAL OF VIROLOGY 93 (4). ScholarBank@NUS Repository. https://doi.org/10.1128/JVI.01457-18
Abstract: Copyright © 2019 Khakpoor et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. Distinct populations of hepatocytes infected with hepatitis B virus (HBV) or only harboring HBV DNA integrations coexist within an HBV chronically infected liver. These hepatocytes express HBV antigens at different levels and with different intracellular localizations, but it is not known whether this heterogeneity of viral antigen expression could result in an uneven hepatic presentation of distinct HBV epitopes/HLA class I complexes triggering different levels of activation of HBV-specific CD8 T cells. Using antibodies specific to two distinct HLA-A*02:01/HBV epitope complexes of HBV nucleocapsid and envelope proteins, we mapped their topological distributions in liver biopsy specimens of two anti-hepatitis B e antigen-positive (HBe) chronic HBV (CHB) patients. We demonstrated that the core and envelope CD8 T cell epitopes were not uniformly distributed in the liver parenchyma but preferentially located in distinct and sometimes mutually exclusive hepatic zones. The efficiency of HBV epitope presentation was then tested in vitro utilizing HLA-A*02:01/HBV epitope-specific antibodies and the corresponding CD8 T cells in primary human hepatocyte and hepatoma cell lines either infected with HBV or harboring HBV DNA integration. We confirmed the existence of a marked variability in the efficiency of HLA class I/HBV epitope presentation among the different targets that was influenced by the presence of gamma interferon (IFN-) and availability of newly translated viral antigens. In conclusion, HBV antigen presentation can be heterogeneous within an HBV-infected liver. As a consequence, CD8 T cells of different HBV specificities might have different antiviral efficacies.
Source Title: JOURNAL OF VIROLOGY
URI: https://scholarbank.nus.edu.sg/handle/10635/160942
ISSN: 0022538X
10985514
DOI: 10.1128/JVI.01457-18
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