Activating Fc gamma receptor (FcγR) (FcγR)

Activating Fc gamma receptors (FcγRs) are a group of cell surface glycoproteins that mediate the interaction between immunoglobulin G (IgG) antibodies and immune effector cells. These receptors, including FcγRI (CD64), FcγRIIa (CD32a), and FcγRIIIa (CD16a), are expressed on cells such as natural killer (NK) cells, macrophages, and neutrophils (Nimmerjahn & Ravetch, 2008). Upon binding to the Fc region of an antibody-antigen complex, activating FcγRs trigger intracellular signaling via immunoreceptor tyrosine-based activation motifs (ITAMs). This signaling leads to critical immune functions such as antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and the release of pro-inflammatory cytokines (Hogarth & Pietersz, 2012). In oncology, many therapeutic monoclonal antibodies, such as rituximab and trastuzumab, utilize these receptors to recruit the host's immune system to destroy tumor cells (Wang et al., 2018). Modern drug development often involves Fc-engineering to enhance the affinity of antibodies for activating FcγRs, particularly FcγRIIIa, to improve clinical outcomes (Bournazos & Ravetch, 2017). Conversely, dysregulation of these receptors is implicated in autoimmune and inflammatory disorders, where they can mediate tissue damage. Therapeutic strategies also include the use of FcγR blockers or decoys to treat such inflammatory conditions. However, the therapeutic use of these receptors must be carefully managed to avoid adverse effects like cytokine release syndrome or systemic inflammation.

Other names

CD64CD32aCD32cCD16aCD16bFc-gamma receptorFCGRLow affinity immunoglobulin gamma Fc region receptorHigh affinity immunoglobulin gamma Fc region receptor I

Engagement of activating FcγRs by the Fc region of monoclonal antibodies to trigger effector cell-mediated killing (ADCC/ADCP) of target cells.