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Activating and Inhibitory Natural Killer Cell Receptors

Natural killer (NK) cells express a variety of receptors that transduce either activating or inhibitory signals. Integration of these signals regulates NK cell effector functions including cytotoxic activity and cytokine secretion. Activating NK cell receptors include members of the human Killer Immunoglobulin-like Receptor (KIR) family or the mouse Ly49 family, CD94-NKG2C/E/H heterodimeric receptors, NKG2D, the nectin and nectin-like binding receptors DNAM-1/CD226 and CRTAM, and natural cytotoxicity receptors such as NKp30, NKp44, and NKp46. In contrast, receptors that inhibit NK cell activation are important for self-tolerance. This group of receptors includes alternate members of the human KIR family or the mouse Ly49 family, CD94-NKG2A, the nectin and nectin-like binding receptors TIGIT and CD96, and ILT2/LILRB1. Several other receptors outside of these families have also been shown to regulate NK cell activity. The sialic acid-binding Siglecs (Siglec-3, -7, and -9), KLRG1, LAIR-1, CD161/NKR-P1A, and CEACAM-1 are additional NK cell inhibitory receptors, while Fc gamma RIIIA/CD16a, CD27, CD100/Semaphorin 4D, and CD160 are additional NK cell activating receptors.