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Interaction of Ly-49D(+) NK cells with H-2D(d) target cells leads to Dap-12 phosphorylation and IFN-gamma secretion

  1. Author:
    Mason, L. H.
    Willette-Brown, J.
    Mason, A. T.
    McVicar, D.
    Ortaldo, J. R.
  2. Author Address

    Mason LH NCI, Expt Immunol Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr Bldg 560,Room 31-93 Frederick, MD 21702 USA NCI, Expt Immunol Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr Frederick, MD 21702 USA
    1. Year: 2000
  1. Journal: Journal of Immunology
    1. 164
    2. 2
    3. Pages: 603-611
  2. Type of Article: Article
  1. Abstract:

    Murine Ly-49D augments NK cell function upon recognition of target cells expressing H-2D(d). Ly-49D activation is mediated by the immunoreceptor tyrosine-based activation moth-containing signaling moiety Dap-12, In this report we demonstrate that Ly-49D receptor ligation can lead to the rapid and potent secretion of IFN-gamma. Cytokine secretion can be induced from Ly-49D(+) NK cells after receptor ligation,vith Ab or after interaction with target cells expressing their H-2D(d) ligand, Consistent with the dominant inhibitory function of Ly-49G, NK cells coexpressing Ly-49D and Ly-49G show a profound reduction in IFN-gamma secretion after interaction with targets expressing their common ligand, H-2D(d). Importantly, we are able to demonstrate for the first time that effector/target cell interactions using Ly-49D(+) NK cells and H-2Dd targets result in the rapid phosphorylation of Dap-12 However, Dap-12 is not phosphorylated when Ly-49D(+) NK cells coexpress the inhibitory receptor, Ly-49G, These studies are novel in describing Ly-49 activation vs inhibition, where two Ly-49 receptors recognize the same class I ligand, with the dominant inhibitory receptor down-regulating phosphorylation of Dap-12, cytokine secretion, and cytotoxicity in NK cells. [References: 37]

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