Antibodies, also called immunoglobulins, are Y-shaped glycoproteins produced by B cells that recognize and neutralize pathogens. They are the effector molecules of humoral immunity, binding with high specificity to antigens through their variable regions.
Basic Structure
All immunoglobulins share a common structural framework consisting of four polypeptide chains: two identical heavy chains and two identical light chains, held together by disulfide bonds and non-covalent interactions. Each chain folds into globular domains called immunoglobulin domains, which consist of about 110 amino acids arranged in a sandwich of two beta sheets stabilized by a conserved disulfide bond, a classic example of protein structure.
The Y-shaped monomer has several regions. The Fab fragments contain the antigen-binding sites, with each arm of the Y forming one binding site. The Fc fragment mediates effector functions including complement activation and receptor binding. The hinge region provides flexibility between the Fab and Fc regions, allowing the two antigen-binding sites to move independently.
Variable and Constant Regions
The N-terminal regions of both heavy and light chains are highly variable between different antibody molecules, forming the variable regions that determine antigen specificity. Within the variable regions, three hypervariable loops called complementarity-determining regions create the antigen-binding surface. The diversity of CDR sequences, generated by VDJ recombination and somatic hypermutation, allows the immune system to recognize a vast array of potential antigens.
The C-terminal regions are constant within each antibody class. The light chain has one constant domain, while the heavy chain has three or four constant domains depending on the isotype. The constant regions determine the antibody class and its effector functions.
Immunoglobulin Classes
Mammals have five immunoglobulin classes. IgG is the most abundant in serum, with four subclasses in humans. It crosses the placenta, providing passive immunity to the fetus, and is the main antibody produced during secondary immune responses. IgM is the first antibody produced during an immune response and exists as a pentamer of five Y-shaped units. Its large size keeps it mainly in the bloodstream, and it is highly effective at activating complement. IgA is the main antibody in mucosal secretions, protecting respiratory, digestive, and reproductive tracts. It exists as a dimer with a J chain. IgE binds to mast cells and basophils and mediates allergic responses and defense against parasites. IgD is found mainly on the surface of naive B cells, functioning as an antigen receptor.
Antigen Binding
Antigen binding occurs through conformational and chemical complementarity between the CDR loops and the antigenic epitope. The interaction involves hydrogen bonds, ionic interactions, van der Waals forces, and hydrophobic interactions. Unlike enzyme-substrate interactions, antibody-antigen binding is typically non-covalent and reversible. Binding affinity is described by the dissociation constant, with high-affinity antibodies having Kd values in the nanomolar to picomolar range.
Effector Functions
The Fc region mediates several effector functions after antigen binding. Antibody-dependent cellular cytotoxicity occurs when Fc receptors on natural killer cells recognize IgG bound to target cells, triggering release of cytotoxic granules. Complement activation begins when IgM or IgG binds antigen, exposing binding sites for C1q and initiating the classical complement cascade. Opsonization involves coating pathogens with IgG, enhancing phagocytosis by macrophages and neutrophils expressing Fc gamma receptors. In mucosal immunity, the polymeric immunoglobulin receptor transports IgA across epithelial cells into secretions.
Monoclonal Antibodies
Monoclonal antibodies are identical antibodies produced by a single B cell clone. They are produced by hybridoma technology, fusing antibody-producing B cells with immortal myeloma cells. Monoclonal antibodies have revolutionized diagnostics (including ELISA) and therapy. Therapeutic monoclonal antibodies treat cancer by blocking growth factor receptors, such as trastuzumab targeting HER2, or by recruiting immune cells through antibody-dependent cellular cytotoxicity. Other therapeutic antibodies block inflammatory cytokines in autoimmune diseases, such as adalimumab targeting tumor necrosis factor.
