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

Virus-specific CD8 T cells are activated when their T cell receptors (TCR) recognize the specific viral-peptide MHC-class I complexes (pMHC) present on the surface of infected cells. Antibodies able to recognize the specific pMHC can mimic TCR specificity and represent both 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 183-91) presented by HLA-A201 molecule and we tested its ability to recognize HBV infected hepatocytes and to deliver a cargo to 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 patients sera and mediates intracellular delivery of a fluorescent molecule to target cells. Additionally, when 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 acid within the epitope. These data demonstrate that a T cell receptor-like antibody can be used to determine the quantitative relation between HBV replication and specific Ag presentation to CD8 T cells and serve as a novel therapeutic delivery platform for personalized health care of HBV infected patients.