Immunoglobulin E (IgE) is an antibody found in mammals, playing a dual role in the body’s immune system. While it helps defend against certain parasitic worms and protozoan infections, IgE is also strongly linked to the development of allergic reactions. Despite being the least abundant antibody type in the bloodstream, at less than 0.0001% of total immunoglobulin concentration, IgE can trigger rapid and severe immune responses, including anaphylaxis.
Overall Architecture of IgE
IgE antibodies exhibit a characteristic “Y” shape. This structure is composed of four protein chains: two identical heavy chains and two identical light chains, linked by disulfide bonds that stabilize the molecule’s form. The “Y” shape divides into two main parts. The two “arms” of the Y are known as the Fragment antigen-binding, or Fab, regions, which are responsible for recognizing and binding to specific foreign substances. The “stem” of the Y is called the Fragment crystallizable, or Fc, region, and interacts with immune cells.
Detailed Components and Their Functions
The Fab regions interact with allergens. Each Fab region is made up of both a heavy and a light chain, each containing a variable and a constant domain. The variable domains are particularly significant because their unique amino acid sequences allow IgE to recognize and bind to a vast array of specific allergens.
The Fc region is composed of the constant domains of the two heavy chains. Unlike the Fab regions, the Fc region’s structure is consistent across all IgE antibodies within a species, regardless of the allergen they target. This region contains four constant domains, labeled Cε1 through Cε4, which are crucial for mediating interactions with other immune system components. The Cε3 domain, in particular, is known to be involved in binding to high-affinity receptors on immune cells.
While IgE lacks a traditional hinge region like some other antibody types, its Fc region exhibits flexibility, with the Cε2 domains capable of extending, twisting, or bending relative to the Cε3-Cε4 region. This inherent flexibility of the Fc region can influence how the antibody interacts with its receptors. Additionally, IgE molecules are glycoproteins, meaning they have sugar groups attached in a process called glycosylation. These sugar modifications are important for the Fc region to properly interact with its receptors and perform its immune functions.
How IgE Structure Governs Allergic Responses
The unique structure of the IgE Fc region allows it to bind with high affinity to specific receptors, primarily FcεRI, found on the surface of mast cells and basophils. This binding sensitizes these immune cells, coating them with allergen-specific IgE antibodies and preparing them to rapidly respond upon subsequent allergen exposure.
When an allergen enters the body, it binds to the Fab regions of the IgE molecules on mast cells. A crucial step for initiating an allergic reaction is that the allergen must bridge at least two IgE molecules on the cell surface. This bridging, known as cross-linking, brings multiple FcεRI receptors together.
The cross-linking of IgE molecules and their associated FcεRI receptors triggers a cascade of internal signals within the mast cell or basophil. This signaling pathway leads to a rapid process called degranulation, where the cells release pre-formed inflammatory mediators stored in their granules. These mediators include substances like histamine and leukotrienes, which are responsible for the various symptoms associated with allergic reactions, such as itching, swelling, and constriction of airways.