Immunoglobulin gamma Fc region (IgG Fc)

The Immunoglobulin gamma Fc (Fragment crystallizable) region is the C-terminal portion of an IgG antibody, composed of the CH2 and CH3 constant domains of the heavy chains. When IgG antibodies coat a target cell by binding to surface antigens, the Fc regions become clustered and accessible, serving as a critical molecular bridge between adaptive and innate immunity (Janeway's Immunobiology, 9th Ed, 2016). This opsonized state allows the Fc region to interact with Fc gamma receptors (FcγRs) on effector cells like Natural Killer (NK) cells and macrophages, triggering Antibody-Dependent Cellular Cytotoxicity (ADCC) and phagocytosis (ADCP). It also binds the C1q component to initiate the classical complement pathway, leading to Complement-Dependent Cytotoxicity (CDC) (Nature Reviews Drug Discovery, 2018, 17:113-133). In therapeutic contexts, the IgG Fc region is a target for engineering to enhance or suppress immune effector functions and to modulate drug half-life via the neonatal Fc receptor (FcRn). Specific drugs like imlifidase (Idefirix) target the Fc region directly by cleaving it to neutralize pathogenic antibodies in transplant rejection and autoimmune crises (EMA Idefirix SmPC, 2020). Furthermore, FcRn inhibitors like efgartigimod (Vyvgart) compete for binding to the Fc region to accelerate the clearance of autoantibodies (FDA Vyvgart Label, 2021). The Fc region on antibody-coated cells is also the functional target for 'universal' CAR-T cells and bispecific engagers designed to recognize the Fc scaffold rather than a specific antigen.

Other names

Fc fragment of IgGCrystallizable fragment of IgGIgG Fc domainImmunoglobulin G FcAntibody Fc region

Engagement of Fc gamma receptors (FcγRs) to trigger effector cell activation; binding to C1q to initiate the classical complement cascade; interaction with FcRn to prevent lysosomal degradation; proteolytic cleavage by endopeptidases to neutralize pathogenic antibodies.