MHC-E-Restricted CD8+ T cells target Hepatitis B virus-infected human hepatocytes

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

doi:10.4049/jimmunol.1900795

MHC-E-Restricted CD8⁺ T cells target Hepatitis B virus-infected human hepatocytes

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

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

Abstract

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, MHCE- restricted CD8⁺ T cells from RM vaccinated with RM CMV vaccine vectors expressing HBVAgs 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.

Original language	English (US)
Pages (from-to)	2169-2176
Number of pages	8
Journal	Journal of Immunology
Volume	204
Issue number	8
DOIs	https://doi.org/10.4049/jimmunol.1900795
State	Published - Apr 15 2020

Funding

This work was supported by Vir Biotechnology (SRA-17-111, to B.J.B.); the Oregon Nanoscience and Microtechnologies Institute (SRA-13-053-B, to K.F.); the National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases under Awards R01 AI144008 (to B.J.B.) and R01 AI117802, R01 AI129703, and R01 AI140888 (to J.B.S.); and the NIH Office of the Director (P51OD011092, to the Oregon National Primate Research Center).

Funders	Funder number
Vir Biotechnology	SRA-17-111
Author National Institutes of Health National Institutes of Health National Institutes of Health National Institutes of Health The Bev Hartig Huntington's Disease Foundation National Institutes of Health
NIH Office of the Director	P51OD011092
National Institute of Allergy and Infectious Diseases	R01AI117802, R01 AI129703, R01 AI144008, R01 AI140888
Oregon National Primate Research Center
Oregon Nanoscience and Microtechnologies Institute	SRA-13-053-B

ASJC Scopus subject areas

Immunology and Allergy
Immunology

Access to Document

10.4049/jimmunol.1900795

Cite this

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., Fruh, K., & Sacha, J. B. (2020). MHC-E-Restricted CD8⁺ T cells target Hepatitis B virus-infected human hepatocytes. Journal of Immunology, 204(8), 2169-2176. https://doi.org/10.4049/jimmunol.1900795

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abstract = "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, MHCE- restricted CD8+ T cells from RM vaccinated with RM CMV vaccine vectors expressing HBVAgs 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.",

author = "Burwitz, \{Benjamin J.\} and Hashiguchi, \{Patrick K.\} and Mandana Mansouri and Christine Meyer and Gilbride, \{Roxanne M.\} and Sreya Biswas and Womack, \{Jennie L.\} and Reed, \{Jason S.\} and Wu, \{Helen L.\} and Axthelm, \{Michael K.\} and Hansen, \{Scott G.\} and Picker, \{Louis J.\} and Klaus Fruh and Sacha, \{Jonah B.\}",

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