Antibody-antigen, biochemical and molecular reactions

Antibodies are produced by the immune system in response to antigens (material perceived as foreign. The antibody response to a particular antigen is highly specific and often involves a physical association between the two molecules. This association is governed by biochemical and molecular forces.

In two dimensions, many antibody molecules present a "Y" shape. At the tips of the arms of the molecules are regions that are variable in their amino acid sequences, depending upon the antigen and the antibody formed in response. The arm-tip regions are typically those that bind to the antigen. These portions of the antibody are also known as the antigenic determinants, or the epitopes.

There are several different types of biochemical interactions between the antibody's epitopes and the target regions on the antigen. Hydrogen bonds are important in stabilizing the antibody-antigen association. In addition, other weak interactions (e.g., van der Waals forces, hydrophobic interactions, electrostatic forces) act to tighten the interaction between the regions on the antibody and the antigen.

The hydrogen bonds that are important in antigen-antibody bonding form between amino acids of the antibody and the antigen. Water molecules that fill in the spaces between the antibody and the antigen create other hydrogen bonds. The formation of hydrogen bonds between other regions of the antibody and antigen , and the water molecules stabilizes the binding of the immune molecules.

The three-dimensional shape of the molecules is also an important factor in binding between an antibody and an antigen. Frequently, the antibody molecule forms a pocket that is the right size and shape to accommodate the target region of the antigen. This phenomenon was initially described as the "lock and key" hypothesis.

The exact configuration of the antibody-antigen binding site is dependent on the particular antigen. Some antigens have a binding region that is compact. Such a region may be able to fit into a pocket or groove in the antibody molecule. In contrast, other antigen sites may be bulky. In this case, the binding site may be more open or flatter.

These various three dimensional structures for the binding site are created by the sequence of amino acids that comprise the antibody protein. Some sequences are enriched in hydrophobic (water-loving) amino acids. Such regions will tend to form flat sheets, with all the amino acids exposed to the hydrophilic environment. Other sequences of amino acids can contain both hydrophilic and hydrophobic (water-hating) amino acids. The latter will tend to bury themselves away from water via the formation of a helical shape, with the hydrophobic region on the inside. The overall shape of an antibody and antigen depends upon the number of hydrophilic and hydrophobic regions and their arrangement within the protein molecule.

The fact that the interaction between an antibody and an antigen requires a specific three-dimensional configuration is exploited in the design of some vaccines. These vaccines consist of an antibody to a region that is present on a so-called receptor protein. Antigens such as toxin molecules recognize the receptor region and bind to it. However, if the receptor region is already occupied by an antibody, then the binding of the antigen cannot occur, and the deleterious effect associated with binding of the antigen is averted.

Antibody antigen reactions tend to be irreversible under normal conditions. This is mainly due to the establishment of the various chemical bonds and interactions between the molecules. The visible clumping of the antibody-antigen complex seen in solutions and diagnostic tests such as the Ochterlony test is an example of the irreversible nature of the association.

See also Immune system; Immunoglobulins and immunoglobulin deficiency syndromes; Laboratory techniques in immunology; Protein crystallography