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CUTTING EDGE |
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852
2B4 is an NK cell activation receptor that can provide a
costimulatory signal to other activation receptors and whose mode of
signal transduction is still unknown. We show that cross-linking of 2B4
on NK cells results in its rapid tyrosine
phosphorylation, implying that this initial step in 2B4
signaling does not require coligation of other receptors. Ligation of
2B4 in the context of an NK cell-target cell interaction leads to 2B4
tyrosine phosphorylation, target cell lysis, and
IFN-
release. Coligation of 2B4 with the inhibitory receptors killer
cell Ig-like receptor (KIR)2DL1 or CD94/NKG2 completely blocks NK cell
activation. The rapid tyrosine phosphorylation of 2B4
observed upon contact of NK cells with sensitive target cells is
abrogated when KIR2DL1 or CD94/NKG2 are engaged by their cognate MHC
class I ligand on resistant target cells. These results demonstrate
that NK inhibitory receptors can interfere with a step as proximal as
phosphorylation of an activation
receptor.
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