TY - JOUR
T1 - PVR (CD155) and Nectin-2 (CD112) as ligands of the human DNAM-1 (CD226) activating receptor
T2 - Involvement in tumor cell lysis
AU - Pende, Daniela
AU - Bottino, Cristina
AU - Castriconi, Roberta
AU - Cantoni, Claudia
AU - Marcenaro, Stefania
AU - Rivera, Paola
AU - Spaggiari, Grazia M.
AU - Dondero, Alessandra
AU - Carnemolla, Barbara
AU - Reymond, Nicolas
AU - Mingari, Maria Cristina
AU - Lopez, Marc
AU - Moretta, Lorenzo
AU - Moretta, Alessandro
PY - 2005/2
Y1 - 2005/2
N2 - 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.
AB - 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.
KW - Activating receptors
KW - Cellular ligands
KW - Natural killer cells
KW - Tumors
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U2 - 10.1016/j.molimm.2004.07.028
DO - 10.1016/j.molimm.2004.07.028
M3 - Article
C2 - 15607800
AN - SCOPUS:10644250886
VL - 42
SP - 463
EP - 469
JO - Molecular Immunology
JF - Molecular Immunology
SN - 0161-5890
IS - 4 SPEC. ISS.
ER -