Antibody Structure: Overview & Insights

Antibodies are made up of two heavy chains and two light chains, bound together to form a Y-shape. The heavy chain delineates the isotype. The tips of the ‘Y’ are called the Fab regions, have an NH2 terminal and contain the antigen-binding sites. The stem is made up of constant regions that determine its effector function and structure; this includes Fc, CH2 and CH3. The hinge region that connects the two arms of the ‘Y’ allows flexibility, which is essential for antigen binding. Overall, antibodies contain four distinct domains; Fab and Fc regions, and light and heavy chains. Each domain plays an important role in antibody structure and function, with the ability to modify this further through mutation to produce tailored antibodies for specific applications.

The Fc region is responsible for effector functions, such as phagocytosis and activating complement proteins. The Fc region comprises of three domains; CH2, CH3 and the hinge region. Soluble antibodies are able to activate effector functions due to their ability to bind cell-surface receptors, such as FcγRIIIa on neutrophils. This interaction triggers a cascade which leads to various biological effects, including promotion of phagocytosis, release of cytokines and induction of apoptosis. Additionally, effector functions can be altered by altering the amino acid residues present in the CH2 and CH3 domains. This allows for tailored antibodies to be designed for specific applications.

The antigen-binding site is located at the tip of the Fab region, adjacent to the NH2 terminal. It is formed by combining the variable domains of both the heavy and light chains. Antibodies are highly specific due to each antibody containing its own unique antigen-binding site. This can be attributed to hypermutation during maturation in order to improve affinity for a particular antigen. Additionally, the complementarity-determining regions (CDRs) are present, which contribute to the specificity of antigen binding. These three loops can be altered by introducing point mutations, thereby allowing for the production of highly specific antibodies with improved affinity for a particular antigen.

Isotypes are determined by the heavy chain constant region, of which four exist in mammalian species: IgM, IgG, IgA and IgE. The differences in the heavy chain domain include the location and quantity of disulfide bonds, length of the hinge region, attached oligosaccharide moieties and the number of constant domains. Furthermore, each isotype is encoded by an individual constant domain gene. Each isotype has its own effector functions and biological roles that are tailored to the particular organism. For example, IgM plays an important role in humoral immunity due to its ability to bind multiple antigens and promote antigen presentation. IgG is the most abundant type of antibody found in blood, and is able to activate complement proteins which leads to increased production of cytokines and lysis of pathogens.

The IgG isotype is the most abundant type of antibody that is found in blood. It has a unique structure and effector functions that are tailored to the particular organism's needs, making it essential for humoral immune responses. IgG antibodies are fruther subdivided into sublasses on account of their corresponding functional activities. IgG1 and IgG3 mediate the immune response in repond to protein antigens. IgG2 and IgG4 are induced by polysaccharide antigens.

The function of IgD is still not fully understood, however it has been suggested to be involved in the regulation of B-cell mediated responses. IgD is expressed primarily on the surface of naïve B cells, and is believed to be important for the initiation of antigen-specific immune response.

IgE is associated with an allergic response and is expressed on the surface of mast cells and basophils. IgE binds to antigen-specific receptors located on specialized cells, thus initiating a series of reactions which culminates in the production and release of histamine and other proinflammatory cytokines. This process is responsible for provoking allergic reactions in people who are predisposed to them.

IgA is the most abundant isotype in mucosal secretions and plays an important role in preventing the attachment of pathogens to epithelial cells. IgA's capacity to bind multiple antigens at once leads to higher antigen presentation and a more vigorous immune system reaction.

IgM is the largest and most intricate antibody, rendering it a formidable tool to identify and neutralize pathogens. Due to its capability of binding numerous antigens at once, IgM antibodies can activate an array of immune responses that consequently eliminate any foreign particles. IgM plays a key role in recognizing foreign bodies, such as bacteria or viruses, and is pivotal for kick-starting an effective immune system response. Yet IgM can also induce aberrant events that may lead to autoimmune diseases; it triggers inflammatory responses which could end up damaging the body's tissues.