Low- and medium-affinity Fc gamma receptors (FcγRII and FcγRIII) (FcγRII/III)

Low- and medium-affinity Fc gamma receptors (FcγRs) are a group of cell surface glycoproteins that bind the Fc region of immunoglobulin G (IgG) antibodies. This group primarily includes FcγRII (CD32) and FcγRIII (CD16), which are expressed on various immune cells such as macrophages, neutrophils, natural killer (NK) cells, and B cells (Nimmerjahn & Ravetch, 2008, Nature Reviews Immunology). Unlike the high-affinity FcγRI, these receptors require the formation of immune complexes or multivalent binding to initiate signaling. They play a critical role in the immune system by bridging the humoral and cellular immune responses, mediating processes like antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and the regulation of antibody production (Bournazos & Ravetch, 2017, Annual Review of Immunology). In therapeutic contexts, many monoclonal antibodies are engineered to optimize their interaction with these receptors to enhance anti-tumor activity or are designed to block inhibitory receptors like FcγRIIB to boost immune responses (Hogarth & Pietersz, 2012, Nature Reviews Drug Discovery). Dysregulation or genetic polymorphisms in these receptors are linked to autoimmune diseases and vary the clinical efficacy of antibody-based therapies. These receptors are also targets for intravenous immunoglobulin (IVIG) therapy, which modulates immune responses in inflammatory conditions. Understanding the balance between activating and inhibitory FcγRs is essential for the development of next-generation biologics with improved safety and efficacy profiles.

Other names

CD32CD16Fc gamma receptor IIFc gamma receptor IIIFc-gamma RIIFc-gamma RIIILow affinity immunoglobulin gamma Fc receptor

Binding of the Fc region of IgG antibodies to these receptors triggers either activating signals via immunoreceptor tyrosine-based activation motifs (ITAM) or inhibitory signals via immunoreceptor tyrosine-based inhibitory motifs (ITIM) to modulate immune effector functions.