Low affinity immunoglobulin gamma Fc receptor IIIa (FCGR3A)

The Low affinity immunoglobulin gamma Fc receptor IIIa, also known as CD16a, is a transmembrane glycoprotein primarily expressed on natural killer (NK) cells, macrophages, and monocytes [UniProt: P08637]. It serves as a critical bridge between the adaptive and innate immune systems by binding the Fc portion of IgG1 and IgG3 antibodies with low affinity [PubMed: 25761023]. Upon activation, it triggers antibody-dependent cellular cytotoxicity (ADCC), a process essential for the clearance of virally infected or malignant cells. In the context of oncology, many therapeutic monoclonal antibodies, such as Rituximab and Trastuzumab, rely on CD16a-mediated ADCC to exert their anti-tumor effects [NIH: PMC4713180]. Clinical studies have shown that a common genetic polymorphism (V158F) in the FCGR3A gene significantly affects the binding affinity of the receptor for IgG, which in turn correlates with the clinical response to various antibody treatments [PubMed: 11830471]. Consequently, drug development efforts often focus on engineering 'Fc-optimized' antibodies or bispecific engagers to maximize the recruitment of CD16a-positive effector cells to tumor sites.

Other names

CD16aFc-gamma RIII-alphaFcRIIIaFCGR3IGFR3CD16A antigen

Binding of the Fc region of IgG antibodies to FCGR3A on immune effector cells (such as NK cells) triggers signaling through immunoreceptor tyrosine-based activation motifs (ITAMs), leading to the release of cytotoxic granules and pro-inflammatory cytokines that destroy target cells (ADCC).