Antibody-Antigen Interactions and the Function of the Fab
The site on the antibody where the antigenic determinant inserts is composed of a hypervariable region whose amino acid content can be extremely varied. Antibodies differ somewhat in the exactness of this groove for antigen, but a certain complementary fit is necessary for the antigen to be held effectively (figure 2). So specific are some immunoglobulins for antigen that they can distinguish between a single functional group of a few atoms. Because the specificity of the Fab sites is identical, an Ig molecule can bind antigenic determinants on the same cell or on two separate cells and thereby link them.
FIGURE 1 Working models of antibody structure. (a) Diagrammatic view of IgG depicts the principal functional areas (Fabs and Fc) of the molecule. (b) Realistic model of immunoglobulin shows the tertiary and quaternary structure achieved by additional intrachain and interchain bonds and the position of the carbohydrate component. (c) The “peanut” model of IgG helps illustrate swiveling of Fabs relative to one another and to Fc.
FIGURE 2 Antigen-antibody binding. The union of antibody (Ab) and antigen (Ag) is characterized by a certain degree of fit and is supported by weak linkages such as hydrogen bonds and electrostatic attraction. (a) In a snug fit such as that shown here, there is great opportunity for attraction and strong attachment. The strength of this union confers high affinity. (b) Examples of the relationship of other antigens with this same antibody. The first Ag clearly cannot be accommodated. The second (purple) antigen is not a perfect fit, but it can bind to the antibody.
The principal activity of an antibody is to unite with, immobilize, call attention to, or neutralize the antigen for which it was formed (figure 3). Antibodies called opsonins stimulate opsonization, a process in which microorganisms or other particles are coated with specific antibodies so that they will be more readily recognized by phagocytes, which dispose of them. Opsonization has been likened to putting handles on a slippery object to provide phagocytes a better grip. The capacity for antibodies to aggregate, or agglutinate, antigens is the consequence of their cross-linking cells or particles into large clumps. The interaction of an antibody with complement can result in the specific rupturing of cells and some viruses. In neutralization reactions, antibodies fill the surface receptors on a virus or the active site on a molecule to prevent it from functioning normally. Antitoxins are a special type of antibody that neutralize bacterial exotoxins. But not all antibodies are protective; some neither benefit nor harm, and a few actually cause autoimmune diseases.
Figure 3 Summary of antibody functions.
Functions of the Crystallizable Fragment
Although the Fab fragments bind antigen, the Fc fragment has a different binding function. In most classes of immunoglobulin, the proximal end of Fc contains an effector molecule that can bind to certain receptors on the membrane of cells, such as macrophages, neutrophils, eosinophils, mast cells, basophils, and lymphocytes. The effect on an antibody’s Fc fragment binding to a cell receptor depends upon that cell’s role. In the case of opsonization, the attachment of antibody to foreign cells and viruses exposes the Fc fragments to phagocytes. Certain antibodies have receptors on the Fc portion for fixing complement, and in some immune reactions, the binding of Fc causes the release of cytokines. For example, the antibody of allergy (IgE) binds to basophils and mast cells, which causes the release of allergic mediators such as histamine. The size and amino acid composition of Fc also determine an antibody’s permeability, its distribution in the body, and its class.