FcRIIA

Fc gamma receptor IIa (FcγRIIa), also known as CD32a, is a low- to intermediate-affinity receptor for the Fc region of immunoglobulin G (IgG). It is encoded by the FCGR2A gene on chromosome 1 and is expressed on cells of the myeloid lineage, including neutrophils, monocytes/macrophages, dendritic cells, and platelets. The receptor preferentially binds IgG1 and IgG3, with binding to IgG2 determined by genetic variants of FCGR2A.

Structurally, FcγRIIa is a transmembrane glycoprotein with two extracellular immunoglobulin-like domains. It signals through association with the Fc receptor gamma chain, which contains an immunoreceptor tyrosine-based activation motif (ITAM). Engagement of FcγRIIa on the surface of effector cells activates signaling pathways that drive phagocytosis, respiratory burst, and release of pro-inflammatory cytokines, contributing to the clearance of opsonized pathogens and immune complexes.

A common feature of FcγRIIa is its genetic polymorphism at residue 131, resulting in H131 or R131 alleles. The H131 variant binds IgG2 more effectively than the R131 variant, influencing opsonophagocytic efficiency and potentially susceptibility to certain infections. FCGR2A polymorphisms have been investigated for associations with autoimmune diseases and responses to monoclonal antibody therapies, with findings that can vary by population and context.

Clinical relevance of FcγRIIa includes its role in antimicrobial defense, immune complex clearance, and modulation of inflammatory responses. It is one of several Fc gamma receptors operating on myeloid cells, contributing to antibody-mediated immunity and therapeutic antibody activity.