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

KSR Sastry, CT Too, K Kaur, AJ Gehring, L Low… - Journal of …, 2011 - Am Soc Microbiol
KSR Sastry, CT Too, K Kaur, AJ Gehring, L Low, A Javiad, T Pollicino, L Li, PTF Kennedy…
Journal of virology, 2011Am Soc Microbiol
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 …
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.
American Society for Microbiology