Published online before print September 8, 2004

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(Journal of Leukocyte Biology. 2004;76:1200-1206.)
© 2004 by Society for Leukocyte Biology

Rat NKp46 activates natural killer cell cytotoxicity and is associated with FcRI and CD3

Ingunn H. Westgaard^*,,1,2, Siri F. Berg^*,2, John T. Vaage, Lawrence L. Wang, Wayne M. Yokoyama, Erik Dissen^* and Sigbjørn Fossum^*

^* Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, Norway;
Department of Medicine, Rheumatology Division, Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri; and
Institute of Immunology, Rikshospitalet University Hospital, Oslo, Norway

¹ Correspondence: Department of Anatomy, University of Oslo, Box 1105 Blindern, N-0317 Oslo, Norway. E-mail: i.h.westgaard{at}basalmed.uio.no

NKp46 has been identified in the human, rat, mouse, monkey, and cattle. We have generated a monoclonal antibody, WEN23, against rat NKp46. By flow cytometry, NKp46 is expressed by all natural killer (NK) cells but not by T cells, B cells, granulocytes, monocytes, dendritic cells, or macrophages. Thus, NKp46/WEN23 is the first NK cell-specific marker in the rat. In a redirected lysis assay, preincubation of the effector cells with WEN23 augmented lysis of the Fc receptor (FcR)⁺ murine tumor target cells, indicating that NKp46 is an activating NK cell receptor. Moreover, preincubation of the effector cells with WEN23 F(ab')₂ fragments reduced killing of target cells, confirming the activating function of NKp46 and indicating that the mouse tumor target cells express a ligand for rat NKp46. Lysis of FcR^– mouse and human tumor target cells was reduced after incubation of effector cells with WEN23, suggesting that rat NKp46 recognizes a ligand that is conserved between primates and rodents. By Western blot and immunoprecipitation using WEN23, NKp46 is expressed as a monomer of 47 kDa in interleukin-2-activated NK cells. The immunoreceptor tyrosine-based activation motif bearing adaptor proteins CD3 and the chain of FcRI for IgE (FcRI) with NKp46 from lysates of NK cells, indicating that rat NKp46 activates NK cell cytotoxicity by similar pathways as CD16.

Key Words: activating receptor • natural cytotoxicity • immunoglobulin superfamily • adaptor protein

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