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MHC-E–Restricted CD8+ T Cells Target Hepatitis B Virus–Infected Human Hepatocytes
Open accessAbstract
Currently 247 million people are living with chronic hepatitis B virus infection (CHB), and the development of novel curative treatments is urgently needed. Immunotherapy is an attractive approach to treat CHB, yet therapeutic approaches to augment the endogenous hepatitis B virus (HBV)–specific T cell response in CHB patients have demonstrated little success. In this study, we show that strain 68-1 rhesus macaque (RM) CMV vaccine vectors expressing HBV Ags engender HBV-specific CD8+ T cells unconventionally restricted by MHC class II and the nonclassical MHC-E molecule in RM. Surface staining of human donor and RM primary hepatocytes (PH) ex vivo revealed the majority of PH expressed MHC-E but not MHC class II. HBV-specific, MHC-E–restricted CD8+ T cells from RM vaccinated with RM CMV vaccine vectors expressing HBV Ags recognized HBV-infected PH from both human donor and RM. These results provide proof-of-concept that MHC-E–restricted CD8+ T cells could be harnessed for the treatment of CHB, either through therapeutic vaccination or adoptive immunotherapy.
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Hepatocytes can present antigens to T cells through MHC-I and trigger antiviral immune responses after murine hepatitis virus B infection.
“Although hepatocytes can present antigens to T cells through MHC-I [94, 95] and trigger antiviral immune responses after murine hepatitis virus B infection [94, 96, 97], the efficacy of local priming in the liver for virus-specific CD8 + T-cell immunity is low, often leading to dysfunctional CD8 + T cells [98, 99].”
From Inflammation and immunity in liver homeostasis and disease: a nexus of hepatocytes, nonparenchymal cells and immune cells (2025) · cites this paper as [96]
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Metadata
- Authors
- Burwitz, B. J., Hashiguchi, P. K., Mansouri, M., Meyer, C., Gilbride, R. M., Biswas, S., Womack, J. L., Reed, J. S., Wu, H. L., Axthelm, M. K., Hansen, S. G., Picker, L. J., Früh, K., & Sacha, J. B.
- Affiliations
- Oregon National Primate Research Center (US)
- Oregon Health & Science University (US)
- VIR Biotechnology (United States) (US)
- Corresponding author
- Mansouri, Mandana
- Biswas, Sreya
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2020-04
- Volume
- 204
- Issue
- 8
- Pages
- 2169-2176
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- PMC
- PMC8109620
- OpenAlex
- W3011870092
- Cited by
- 24
- References
- 38
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 4 · 2023: 3 · 2022: 5 · 2021: 3 · 2020: 2
- FWCI
- 2.33
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Vir Biotechnology (SRA-17-111)
- Oregon Nanoscience and Microtechnologies Institute (SRA-13-053-B)
- National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (R01 AI144008, R01 AI117802, R01 AI129703, R01 AI140888)
- NIH Office of the Director (P51OD011092)
- Topics
- Health Sciences › Medicine › Epidemiology › Hepatitis B Virus Studies
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- CD8+ T cells, hepatitis B virus, chronic hepatitis B, hepatocytes, therapeutic vaccination, adoptive immunotherapy
- MeSH terms
- Animals, Hepatitis B virus, Macaca mulatta, Histocompatibility Antigens Class I, CD8-Positive T-Lymphocytes, Hepatitis B, Chronic, Hepatocytes
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