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 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.
Pende
Daniela
D
Istituto Nazionale per la Ricerca sul Cancro, L.go R. Benzi 10, 16132 Genova, Italy. daniela.pende@istge.it
Bottino
Cristina
C
Castriconi
Roberta
R
Cantoni
Claudia
C
Marcenaro
Stefania
S
Rivera
Paola
P
Spaggiari
Grazia M
GM
Dondero
Alessandra
A
Carnemolla
Barbara
B
Reymond
Nicolas
N
Mingari
Maria Cristina
MC
Lopez
Marc
M
Moretta
Lorenzo
L
Moretta
Alessandro
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D019556:COS Cells; D015815:Cell Adhesion Molecules / Q000302:isolation & purification / Q000378:metabolism*; D002522:Chlorocebus aethiops; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D008565:Membrane Proteins / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D000075983:Nectins; D009369:Neoplasms / Q000276:immunology*; D010449:Peptide Mapping; D011991:Receptors, Virus / Q000302:isolation & purification / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D000098862:T Lineage-Specific Activation Antigen 1
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1; D015815:Cell Adhesion Molecules; D007141:Immunoglobulin Fc Fragments; D008024:Ligands; D008565:Membrane Proteins; D000075983:Nectins; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; C066100:poliovirus receptor