Interaction of Ly-49D+ NK cells with H-2Dd target cells leads to Dap-12 phosphorylation and IFN-γ secretion

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.