MHC-E–Restricted CD8+ T Cells Target Hepatitis B Virus–Infected Human Hepatocytes | Zendy

Benjamin J. Burwitz | Zendy; Patrick K Hashiguchi | Zendy; Mandana Mansouri | Zendy; Christine Meyer | Zendy; Roxanne M. Gilbride | Zendy; Sreya Biswas | Zendy; Jennie Womack | Zendy; Jason S. Reed | Zendy; Helen L. Wu | Zendy; Michael K. Axthelm | Zendy; Scott G. Hansen | Zendy; Louis J. Picker | Zendy; Klaus Früh | Zendy; Jonah B. Sacha | Zendy

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MHC-E–Restricted CD8+ T Cells Target Hepatitis B Virus–Infected Human Hepatocytes

Author(s) -

Benjamin J. Burwitz,

Patrick K Hashiguchi,

Mandana Mansouri,

Christine Meyer,

Roxanne M. Gilbride,

Sreya Biswas,

Jennie Womack,

Jason S. Reed,

Helen L. Wu,

Michael K. Axthelm,

Scott G. Hansen,

Louis J. Picker,

Klaus Früh,

Jonah B. Sacha

Publication year - 2020

Publication title -

the journal of immunology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.737

H-Index - 372

eISSN - 1550-6606

pISSN - 0022-1767

DOI - 10.4049/jimmunol.1900795

Subject(s) - virology , mhc class i , cd8 , hepatitis b virus , immunology , cytotoxic t cell , immunotherapy , major histocompatibility complex , t cell , biology , medicine , antigen , virus , immune system , in vitro , biochemistry

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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