Fc region

Structurally, an immunoglobulin molecule is Y-shaped, consisting of two heavy chains and two light chains. The 'arms' of the Y form two identical Fab (fragment antigen-binding) regions, each containing a variable domain that binds specific antigen. The 'stem' of the Y is the Fc region, formed by the constant (CH2-CH3, and CH4 for IgM/IgE) domains of the two heavy chains joined by disulfide bonds.

Functions of the Fc region: 1. Effector cell binding: Fc receptors (FcγR on macrophages, neutrophils, NK cells; FcεRI on mast cells/basophils; FcαR on neutrophils) recognize the Fc region, triggering phagocytosis (opsonization), antibody-dependent cellular cytotoxicity (ADCC), and degranulation (e.g., IgE-mediated mast cell activation in type I hypersensitivity). 2. Complement activation: The Fc region of IgM and IgG (particularly IgG1 and IgG3) binds C1q, initiating the classical complement pathway. 3. Placental transfer: The Fc region of IgG binds the neonatal Fc receptor (FcRn), allowing transplacental passage of maternal IgG to the fetus, providing passive immunity. 4. Determines antibody isotype/class (IgG, IgA, IgM, IgD, IgE) and subclass-specific functions. 5. Glycosylation of the Fc region affects its function and is exploited therapeutically.

Clinical relevance: - Monoclonal antibody therapeutics (e.g., rituximab, trastuzumab) are engineered with Fc regions to promote ADCC and complement-mediated cytotoxicity against target cells. - IVIG (intravenous immunoglobulin) therapy works partly by saturating Fc receptors, used in autoimmune conditions like ITP and Kawasaki disease. - Fc receptor polymorphisms can affect susceptibility to autoimmune diseases and response to antibody therapies. - Protein A and Protein G (from Staphylococcus aureus and Streptococcus) bind the Fc region and are used in immunoprecipitation and antibody purification techniques. - Understanding Fc-FcR interactions is essential for understanding hypersensitivity reactions (Type I-III) and vaccine design.