Immunoglobulin G1 (IgG1) is the most common antibody in human circulation and tissue fluids. As a component of the adaptive immune system, its primary role is to recognize and neutralize foreign entities like bacteria and viruses. When an IgG1 molecule identifies a matching foreign structure, it initiates a targeted response to eliminate the invader.
Fundamental Building Blocks of IgG1
The IgG1 molecule is a glycoprotein with a “Y” shaped architecture. It is assembled from four polypeptide chains: two identical heavy chains and two identical light chains. The chains are arranged symmetrically, with one light chain associated with each heavy chain.
This assembly is held together by covalent linkages called disulfide bonds, which form between specific amino acids on the different chains. These bonds maintain the antibody’s structural integrity. One disulfide bond connects each light chain to its corresponding heavy chain, while additional bonds link the two heavy chains in the central part of the molecule.
The polypeptide chains are organized into distinct sections called domains. Each light chain contains one variable and one constant domain. Each heavy chain is composed of one variable domain and three constant domains. This modular construction of variable and constant regions is what creates the different functional parts of the antibody.
The Antigen-Binding Region
The two arms of the Y-shaped IgG1 molecule are its antigen-binding fragments, known as the Fab regions. Each IgG1 molecule has two identical Fab regions, allowing it to bind to two identical targets at once. This part of the antibody recognizes and latches onto a specific molecular structure, called an antigen, on a pathogen’s surface.
The specificity of this interaction is determined by the variable domains at the tip of each Fab arm. These domains, one from the heavy chain (VH) and one from the light chain (VL), form the antigen-binding site. The amino acid sequences in these variable domains differ greatly between antibodies, which allows the immune system to produce IgG1 molecules that can recognize a vast array of antigens.
Within the variable domains are hypervariable loops known as complementarity-determining regions (CDRs). These CDRs form the precise three-dimensional surface that makes direct contact with the antigen. The unique shape and chemical properties of this surface allow it to fit a specific antigen with high precision, an interaction often compared to a lock and key.
The Effector Function Region
The stem of the Y-shaped IgG1 molecule is the Fragment, crystallizable (Fc) region. Composed of segments from the two heavy chains, this region becomes active after the Fab arms bind to a target. The Fc region’s purpose is to communicate with other parts of the immune system, acting as a flag to signal that a target needs to be eliminated.
This communication occurs when the Fc region binds to specialized proteins on other immune cells, known as Fc receptors. Cells like macrophages, neutrophils, and natural killer (NK) cells possess these receptors. When the Fc region of an antibody-coated pathogen engages these receptors, it triggers defensive actions. These include phagocytosis, where a macrophage engulfs the pathogen, and antibody-dependent cell-mediated cytotoxicity (ADCC), where an NK cell releases toxic substances to kill the target.
A feature of the Fc region that influences these interactions is glycosylation, the attachment of complex sugar chains. A specific site on each heavy chain within the Fc region has a conserved glycan structure. Variations in this glycan’s composition can alter the Fc region’s shape. This change affects how tightly it binds to Fc receptors, which modulates the strength and type of the immune response.
The Hinge Region and Structural Flexibility
Connecting the two Fab arms to the Fc stem is a flexible stretch of the heavy chains known as the hinge region. This segment is rich in amino acids like proline, which impart a high degree of motion. This flexibility allows the two Fab arms to move independently of each other and the Fc stem.
The movement permitted by the hinge allows the Fab arms to open, close, and rotate to effectively bind to antigens. Pathogens often display multiple copies of an antigen on their surface with irregular spacing. The hinge’s flexibility enables a single IgG1 molecule to bind to two separate antigen sites on one pathogen, even if the spacing is not ideal.
This ability to bind two sites simultaneously increases the overall binding strength of the antibody to its target, a concept known as avidity. By forming a more stable connection with a pathogen, the IgG1 molecule is less likely to detach once it has bound. This secure attachment ensures the pathogen remains tagged for clearance by the immune system.