PVR (CD155) and Nectin-2 (CD112) as Ligands of the Human DNAM-1 (CD226) Activating Receptor: Involvement in Tumor Cell Lysis

Mol Immunol. 2005 Feb;42(4):463-9. doi: 10.1016/j.molimm.2004.07.028.

Abstract

The capability of NK lymphocytes to kill tumor cells depends on different receptors/ligands interactions. In order to identify the cellular ligands recognized by "orphan" triggering receptors, mice were immunized with NK susceptible target cells. mAbs were selected that inhibited NK cytotoxicity and recognized two different molecules of 70 and 60-65 kDa. Tryptic digestion and mass spectra analysis of purified proteins identified these molecules as PVR and Nectin-2, respectively. PVR-Fc and Nectin-2-Fc chimeric molecules stained COS-7 cells expressing the DNAM-1 activating receptor and conversely, PVR and Nectin-2 CHO-K cell transfectants were stained by DNAM-1-Fc. Thus, both PVR and Nectin-2 represent specific ligands for DNAM-1. Importantly, the specific interaction between DNAM-1 (in NK cells) and PVR or Nectin-2 (in target cells) enhanced the NK-mediated lysis of tumor cells that was downregulated by mAb-mediated masking of the receptor or its ligands.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antigens, Differentiation, T-Lymphocyte / metabolism*
  • COS Cells
  • Cell Adhesion Molecules / isolation & purification
  • Cell Adhesion Molecules / metabolism*
  • Chlorocebus aethiops
  • Cytotoxicity, Immunologic
  • Humans
  • Immunoglobulin Fc Fragments / immunology
  • Killer Cells, Natural / immunology*
  • Ligands
  • Membrane Proteins / isolation & purification
  • Membrane Proteins / metabolism*
  • Mice
  • Nectins
  • Neoplasms / immunology*
  • Peptide Mapping
  • Receptors, Virus / isolation & purification
  • Receptors, Virus / metabolism*
  • Recombinant Fusion Proteins / immunology

Substances

  • Antibodies, Monoclonal
  • Antigens, Differentiation, T-Lymphocyte
  • CD226 antigen
  • Cell Adhesion Molecules
  • Immunoglobulin Fc Fragments
  • Ligands
  • Membrane Proteins
  • Nectins
  • Receptors, Virus
  • Recombinant Fusion Proteins
  • poliovirus receptor