Targeting hepatitis B virus-infected cells with a T-cell receptor-like antibody

J Virol. 2011 Mar;85(5):1935-42. doi: 10.1128/JVI.01990-10. Epub 2010 Dec 15.

Abstract

Virus-specific CD8 T cells are activated when their T-cell receptors (TCRs) recognize the specific viral peptide/major histocompatibility complex (MHC) class I (pMHC) complexes present on the surface of infected cells. Antibodies able to recognize the specific pMHC can mimic TCR specificity and both represent a valuable biological tool to visualize pMHC complexes on infected cells and serve as a delivery system for highly targeted therapies. To evaluate these possibilities, we created a monoclonal antibody able to specifically recognize a hepatitis B virus (HBV) envelope epitope (Env at positions 183 to 91 [Env183-91]) presented by the HLA-A201 molecule, and we tested its ability to recognize HBV-infected hepatocytes and to deliver a cargo to a specific target. We demonstrate that this antibody detects and visualizes the processed product of HBV proteins produced in naturally HBV-infected cells, is not inhibited by soluble HBV proteins present in patient sera, and mediates the intracellular delivery of a fluorescent molecule to target cells. Additionally, compared to CD8 T cells specific for the same HBV epitope, the TCR-like antibody has both a superior sensitivity and a specificity focused on distinct amino acids within the epitope. These data demonstrate that a T-cell receptor-like antibody can be used to determine the quantitative relationship between HBV replication and specific antigen presentation to CD8 T cells and serves as a novel therapeutic delivery platform for personalized health care for HBV-infected patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / immunology*
  • Antibodies, Viral / therapeutic use
  • Antigen Presentation
  • Cell Line
  • Hepatitis B / drug therapy
  • Hepatitis B / immunology*
  • Hepatitis B / virology
  • Hepatitis B virus / immunology*
  • Hepatitis B virus / physiology
  • Hepatocytes / immunology
  • Hepatocytes / virology
  • Humans
  • Mice
  • Receptors, Antigen, T-Cell / immunology*
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology

Substances

  • Antibodies, Viral
  • Receptors, Antigen, T-Cell
  • Viral Envelope Proteins