PVR (CD155) and Nectin-2 (CD112) as ligands of the human DNAM-1 (CD226) activating receptor: involvement in tumor cell lysis

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...

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Bibliographic Details
Published in:Molecular immunology 2005-02, Vol.42 (4), p.463-469
Main Authors: Pende, Daniela, Bottino, Cristina, Castriconi, Roberta, Cantoni, Claudia, Marcenaro, Stefania, Rivera, Paola, Spaggiari, Grazia M., Dondero, Alessandra, Carnemolla, Barbara, Reymond, Nicolas, Mingari, Maria Cristina, Lopez, Marc, Moretta, Lorenzo, Moretta, Alessandro
Format: Article
Language:English
Subjects:
Activating receptors
Animals
Antibodies, Monoclonal - immunology
Antigens, Differentiation, T-Lymphocyte - metabolism
Cell Adhesion Molecules - isolation & purification
Cell Adhesion Molecules - metabolism
Cellular ligands
Cercopithecus aethiops
COS Cells
Cytotoxicity, Immunologic
Humans
Immunoglobulin Fc Fragments - immunology
Killer Cells, Natural - immunology
Ligands
Membrane Proteins - isolation & purification
Membrane Proteins - metabolism
Mice
Natural killer cells
Nectins
Neoplasms - immunology
Peptide Mapping
Receptors, Virus - isolation & purification
Receptors, Virus - metabolism
Recombinant Fusion Proteins - immunology
Tumors
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Summary: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.
ISSN:0161-5890
1872-9142
DOI:10.1016/j.molimm.2004.07.028