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

J Immunol. 2020 Apr 15;204(8):2169-2176. doi: 10.4049/jimmunol.1900795. Epub 2020 Mar 11.

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, 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Hepatitis B virus / immunology*
  • Hepatitis B, Chronic / immunology*
  • Hepatitis B, Chronic / virology
  • Hepatocytes / immunology*
  • Hepatocytes / virology
  • Histocompatibility Antigens Class I / immunology*
  • Macaca mulatta

Substances

  • Histocompatibility Antigens Class I