Antibodies are proteins in the immune system that identify and neutralize foreign substances like bacteria and viruses. An antibody’s structure is directly related to its function, and a primary characteristic is the number of sites it uses to attach to a target. This article focuses on bivalent antibodies, which are distinguished by having two such binding sites.
Understanding Antibody Valency
The term “valency” refers to the number of antigen-binding sites a single antibody molecule possesses. Bivalency, meaning the presence of two antigen-binding sites, is a common arrangement for many antibody types circulating in the body.
In contrast, some antibody fragments are monovalent, possessing only one binding site. Other antibody types are multivalent, meaning they have more than two binding sites. An example is the IgM antibody class, which can form a structure with ten binding sites.
The Classic Bivalent Structure
The archetypal bivalent antibody is Immunoglobulin G (IgG), the most abundant antibody in blood serum. Its structure is a “Y” shape, composed of four polypeptide chains: two identical heavy chains and two identical light chains linked by disulfide bonds.
At the tips of the two upper arms of the “Y” are the antigen-binding sites. Each arm is known as a Fab (fragment, antigen-binding) region, formed by the combination of a light chain and the end of a heavy chain. These sites are shaped to recognize and bind to a specific part of a foreign substance, known as an epitope.
The stem of the “Y” is called the Fc (fragment, crystallizable) region and is composed of the remaining parts of the two heavy chains. This region does not bind to antigens but interacts with other components of the immune system, like receptors on immune cells. Connecting the Fab arms to the Fc stem is a flexible hinge region that allows the two arms to move, adjusting their orientation to bind to targets.
Functional Advantages of Bivalency
Having two antigen-binding sites provides functional benefits over a monovalent structure. A primary advantage is an increase in the overall binding strength, a concept known as avidity. While affinity is the strength of a single binding site’s interaction, avidity is the combined strength of all sites. The bivalent design means that if one binding site detaches, the other can hold on, making the connection more stable.
This dual-binding capability allows bivalent antibodies to perform cross-linking. When an antibody encounters multiple copies of the same antigen, like on the surface of a bacterium, it can bind to two separate antigen molecules at once. This action links the pathogens together, causing them to clump in a process called agglutination, making them easier for immune cells to eliminate.
The cross-linking of antigens also forms immune complexes. The formation of these complexes can trigger other defense mechanisms, such as the complement system, a cascade of proteins that can destroy pathogens. Bivalent binding enhances the activation of this system, leading to a more effective immune response.
Bivalent Antibodies in Nature and Medicine
Natural Bivalent Antibodies
In the body’s natural immune response, several classes of antibodies exist in a bivalent form. Immunoglobulin G (IgG) is the most prominent, circulating throughout the blood and tissues to provide long-term protection. Other examples include the monomeric form of Immunoglobulin A (IgA) found in serum and the monomeric form of Immunoglobulin M (IgM), which acts as a receptor on the surface of B cells.
Therapeutic Monoclonal Antibodies
The bivalent structure serves as a model for medical treatments. Many therapeutic monoclonal antibodies (mAbs) are laboratory-produced molecules engineered as bivalent IgG molecules to target specific cells or proteins. This design is used in cancer treatments, where the antibodies bind to tumor cells and mark them for destruction. In autoimmune diseases, mAbs can be designed to bind and neutralize proteins that cause inflammation.
Advanced Antibody Engineering
Modern antibody engineering has built upon the bivalent principle to create new therapeutic tools. Bispecific antibodies, for example, are engineered molecules that have a bivalent structure but with two different binding sites. Instead of binding to two identical epitopes, one arm can bind to a target like a cancer cell, while the other arm binds to an immune cell. This brings the two together to initiate a targeted attack.