Rat NKp46 activates natural killer cell cytotoxicity and is associated with FcεRIγ and CD3ζ

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

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

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 CD3ζ and the γ chain of FcRI for IgE (FcεRIγ) with NKp46 from lysates of NK cells, indicating that rat NKp46 activates NK cell cytotoxicity by similar pathways as CD16.

Original languageEnglish
Pages (from-to)1200-1206
Number of pages7
JournalJournal of Leukocyte Biology
Volume76
Issue number6
DOIs
StatePublished - Dec 2004

Keywords

  • Activating receptor
  • Adaptor protein
  • Immunoglobulin superfamily
  • Natural cytotoxicity

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