HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Stern-Ginossar, N. Articles by Mandelboim, O. Search for Related Content PubMed PubMed Citation Articles by Stern-Ginossar, N. Articles by Mandelboim, O.

Intercellular Transfer of Carcinoembryonic Antigen from Tumor Cells to NK Cells¹

Noam Stern-Ginossar^*, Shlomo Nedvetzki, Gal Markel, Roi Gazit^*, Gili Betser-Cohen^*, Hagit Achdout^*, Memet Aker, Richard S. Blumberg^¶, Daniel M. Davis, Ben Appelmelk^|| and Ofer Mandelboim^2,*

^* Lautenberg Center for General and Tumor Immunology, Hadassah Medical School, Hebrew University, Jerusalem, Israel; Division of Cell and Molecular Biology, Imperial College, London, United Kingdom; Ella Institute for Melanoma Research, Sheba Cancer Research Center, Sheba Medical Center, Tel Hashomer, Israel; Department of Pediatrics, Hadassah University Hospital, Jerusalem, Israel; ^¶ Gastroenterology Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115; and ^|| Department of Medical Microbiology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from The U.S.–Israel Bi-National Science Foundation (to O.M.), by grants from The Israeli Cancer Research Foundation (to O.M.), by a grant from The Israeli Science Foundation (O.M.), by grants from the European Consortium (MRTN-CT-2005 and LSCH-CT-2005-518178, to O.M.), and by a grant from the Association for International Cancer Research. N. S.-G. is supported by the Adams Fellowship Program of the Israil Academy of Sciences and Humanities.

² Address correspondence and reprint requests to Dr. Ofer Mandelboim, Lautenberg Center for General and Tumor Immunology, Hadassah Medical School, Hebrew University, Jerusalem, Israel. E-mail address: oferm{at}ekmd.huji.ac.il

³ Abbreviations used in this paper: KIR, killer Ig-like receptor; CEA, carcinoembryonic Ag; CEACAM, CEA cell adhesion molecule; DC-SIGN, dendritic cell-specific ICAM-3-grabbing nonintegrin; LeX, Lewis X; YFP, yellow fluorescent protein; MICA, major histocompatibility complex class I-related chain A.