Fragment crystallizable region of immunoglobulin G (IgG Fc region) (Fc region)

The Fragment crystallizable (Fc) region is the tail portion of an immunoglobulin molecule, primarily IgG, that mediates the antibody's effector functions by interacting with various cell surface receptors and the complement system [1, 3]. It consists of two identical protein fragments derived from the second and third constant domains of the antibody's heavy chains [3, 9]. In the context of therapeutic monoclonal antibodies, the Fc region is a critical structural component that determines the drug's serum half-life through its pH-dependent interaction with the neonatal Fc receptor (FcRn) [5, 18]. It also dictates the antibody's ability to recruit immune effector cells for processes such as antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) [1, 9]. Therapeutic engineering of the Fc region, including glycoengineering and site-specific mutations, is widely used to optimize these effector functions or to silence them to reduce toxicity [6, 12]. Additionally, the Fc region itself can be a target for enzymatic cleavage by drugs like imlifidase, which is used to rapidly deplete pathogenic antibodies in transplant and autoimmune settings [13].

Other names

Fc fragmentFc domainFragment crystallizable regionIgG Fc regionAntibody tail region

Drugs targeting the Fc region, such as imlifidase, act by enzymatic cleavage of the IgG hinge region to neutralize pathogenic antibodies [13]. In the context of therapeutic antibody design, the Fc region is engineered via mutations or glycoengineering to modulate its interaction with Fc receptors (FcγRs) and the neonatal Fc receptor (FcRn), thereby enhancing or silencing effector functions and extending serum half-life [6, 9, 12].