Inhibitory Ly49 receptors on mouse natural killer cells

The Ly49 receptors, which are expressed in a stochastic manner on subsets of murine natural killer (NK) cells, T cells, and other cells, are encoded by the Klra gene family and include receptors with either inhibitory or activating function. All of the inhibitory Ly49 receptors are characterized by an immunoreceptor tyrosine-based inhibitory motif in their cytoplasmic domain, which upon phosphorylation recruits tyrosine or lipid phosphatases to dampen signals transmitted through other activating receptors. Most of the inhibitory Ly49 receptors recognize polymorphic epitopes on major histocompatibility complex (MHC) class I proteins as ligands. Here, we review the polymorphism, ligand specificity, and signaling capacity of the inhibitory Ly49 receptors and discuss how these molecules regulate NK cell development and function.