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

Konduru S.R. Sastry, Chien Tei Too, Kaval Kaur, Adam J. Gehring, Lionel Low, Alia Javiad, Teresa Pollicino, Li Li, Patrick T.F. Kennedy, Uri Lopatin, Paul A. Macary, Antonio Bertoletti

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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.

Original languageEnglish
Pages (from-to)1935-1942
Number of pages8
JournalJournal of Virology
Volume85
Issue number5
DOIs
Publication statusPublished - 1 Mar 2011

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ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Sastry, K. S. R., Too, C. T., Kaur, K., Gehring, A. J., Low, L., Javiad, A., Pollicino, T., Li, L., Kennedy, P. T. F., Lopatin, U., Macary, P. A., & Bertoletti, A. (2011). Targeting hepatitis B virus-infected cells with a T-cell receptor-like antibody. Journal of Virology, 85(5), 1935-1942. https://doi.org/10.1128/JVI.01990-10