Ig-binding Receptors on Human NK Cells as Effector and Regulatory Surface Molecules

The receptors on human natural killer 9NK cells which can specifically bind the Fc portion of immunoglobulin molecules (Fc receptors) have been extensively studied. The best known and studied Fc receptor on human NK cells is FcgammaRIIIa. Interactions of NK cells with IgG antibodies via this receptor are well known to induce a signal transduction cascade and lead to antibody-dependent cell-mediated cytotoxicity (ADCC) as well as release of various cytokines. In addition, interactions with monomeric IgG and FcgammaRIIIa have been demonstrated, which result in negative regulation of NK activity and other immunomodulatory effects. Over the past several years, it has also become increasingly appreciated that human NK cells express a variety of other Fc receptors, including FcmuR, which also can mediate effector and immunoregulatory functions. Also, a novel form of FcgammaR has been demonstrated on human NK cells, termed FcgammaRIIc. Recent molecular studies have shown considerable polymorphism in the genes for FcgammaIIc and the functional consequences are being dissected. This appears to include cross-talk between FcgammaRIIIa and at least some forms of FcgammaRIIc, which may have important functional consequences.