Intercellular transfer of carcinoembryonic antigen from tumor cells to NK cells.
The inhibition of NK cell killing is mainly mediated via the interaction of NK inhibitory receptors with MHC class I proteins. In addition, we have previously demonstrated that NK cells are inhibited in a class I MHC-independent manner via homophilic carcinoembryonic Ag (CEA) cell adhesion molecules (CEACAM1)-CEACAM1 and heterophilic CEACAM1-CEA interactions. However, the cross-talk between immune effector cells and their target cells is not limited to cell interactions per se, but also involves a specific exchange of proteins. The reasons for these molecular exchanges and the functional outcome of this phenomenon are still mostly unknown. In this study, we show that NK cells rapidly and specifically acquire CEA molecules from target cells. We evaluated the role of cytotoxicity in the acquisition of CEA and demonstrated it to be mostly killing independent. We further demonstrate that CEA transfer requires a specific interaction with an unknown putative NK cell receptor and that carbohydrates are probably involved in CEA recognition and acquisition by NK cells. Functionally, the killing of bulk NK cultures was inhibited by CEA-expressing cells, suggesting that this putative receptor is an inhibitory receptor.
Stern-Ginossar
Noam
N
Lautenberg Center for General and Tumor Immunology, Hadassah Medical School, Hebrew University, Jerusalem, Israel.
Nedvetzki
Shlomo
S
Markel
Gal
G
Gazit
Roi
R
Betser-Cohen
Gili
G
Achdout
Hagit
H
Aker
Memet
M
Blumberg
Richard S
RS
Davis
Daniel M
DM
Appelmelk
Ben
B
Mandelboim
Ofer
O
D017209:Apoptosis; D050260:Carbohydrate Metabolism; D002241:Carbohydrates / Q000737:chemistry; D002272:Carcinoembryonic Antigen / Q000737:chemistry / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D015236:HLA-C Antigens / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*; D019899:Paracrine Communication
D002241:Carbohydrates; D002272:Carcinoembryonic Antigen; D015236:HLA-C Antigens; C528994:HLA-C*06 antigen