title: Targeting hepatitis B virus-infected cells with a T-cell receptor-like antibody.
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.
authors.affiliation: Singapore Institute for Clinical Sciences, Singapore 117609, Republic of Singapore.
authors.forename: Konduru S R
authors.initials: KS
authors.lastname: Sastry
authors.forename: Chien Tei
authors.initials: CT
authors.lastname: Too
authors.forename: Kaval
authors.initials: K
authors.lastname: Kaur
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Gehring
authors.forename: Lionel
authors.initials: L
authors.lastname: Low
authors.forename: Alia
authors.initials: A
authors.lastname: Javiad
authors.forename: Teresa
authors.initials: T
authors.lastname: Pollicino
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Patrick T F
authors.initials: PT
authors.lastname: Kennedy
authors.forename: Uri
authors.initials: U
authors.lastname: Lopatin
authors.forename: Paul A
authors.initials: PA
authors.lastname: Macary
authors.forename: Antonio
authors.initials: A
authors.lastname: Bertoletti
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology* / Q000627:therapeutic use; D017951:Antigen Presentation; D002460:Cell Line; D006509:Hepatitis B / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D006515:Hepatitis B virus / Q000276:immunology* / Q000502:physiology; D022781:Hepatocytes / Q000276:immunology / Q000821:virology; D006801:Humans; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D011948:Receptors, Antigen, T-Cell; D014759:Viral Envelope Proteins