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Killer Immunoglobulin-like Receptors (KIRs)

Killer immunoglobulin-like receptors (KIRs) are a highly polymorphic family of natural killer cell receptors that interact with MHC class I molecules and elicit inhibitory, activating, or dual signals. KIRs are named for the number of Ig-like domains (2D or 3D) that they contain in their extracellular regions and the presence of a long or short (L or S) cytoplasmic tail. Those with a long cytoplasmic tail contain one or two immunoreceptor tyrosine-based inhibitory motif (ITIM) domains through which they associate with downstream effector molecules that inhibit NK cell activation. In contrast, those with a short cytoplasmic tail associate with FcRgamma or Dap12, two adaptor proteins that contain an immunoreceptor tyrosine-based activation motif (ITAM) and trigger signaling pathways that promote NK cell activation. KIRs are not present in mice, but similar functions are carried out by the Ly49 receptors. Like KIRs, Ly49 receptors recognize MHC class I and class I-like molecules on normal and altered cells and can have either inhibitory or activating functions.