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Secretion1
Laboratory of Experimental Immunology, Division of Basic Sciences, National Cancer Institute, Frederick, MD 21702
Murine Ly-49D augments NK cell function upon recognition of target
cells expressing H-2Dd. Ly-49D activation is mediated by
the immunoreceptor tyrosine-based activation motif-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-
.
Cytokine secretion can be induced from Ly-49D+ NK cells
after receptor ligation with Ab or after interaction with target cells
expressing their H-2Dd ligand. Consistent with the dominant
inhibitory function of Ly-49G, NK cells coexpressing Ly-49D and Ly-49G
show a profound reduction in IFN- secretion after interaction with
targets expressing their common ligand, H-2Dd. 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.
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