Antibody-antigen interaction

Many molecules are capable of giving rise to an immune response, i.e. they are antigens. Each molecule has a unique shape. It is this shape which gives rise to the specificity of the antigen-antibody reaction. Clearly larger and more complex molecules may have several different regions, each of which is capable of binding an antibody. Such regions are known as antigenic determinants or epitopes. It is possible for one antigenic molecule to contain several epitopes. Smaller antigens, on the other hand, may possess only one epitope. The basis of the antibody-antigen interaction is the fitting together of two molecules of complementary shape. The shape of the antigen is determined by the three dimensional structure of the molecule. All immunoglobulin molecules have a similar basic structure consisting of two heavy and two light chains held together by disulphide bonds (Fig. 1.1).

Fig. 1.1. Structure of IgG. The variable region and antigen-binding sites are at the N-terminus of the peptide chains.

Antibodies have areas in the heavy and light chains known as variable regions in which the amino acid sequence of the protein chain varies from one antibody to another. This variation occurs at the N-terminus of the peptide chains. Each different antibody will therefore have a different amino acid sequence and spatial arrangement. It is therefore conceivable that every possible shape presented by an antigen can be accommodated by some antibody produced by the immune system (Fig 1.2).

Fig. 1.2. Schematic diagram showing binding of an antigenic determinant to a binding site at the N-terminus of an antibody molecule

The mechanisms in which such a diverse series of proteins are generated from a limited amount of information encoded in the DNA of an individual has received considerable attention over recent years. The genes that code for different chains of the immunoglobulin are located at different sites of the genome. In addition, there are several constant region and variable region domains within each chain, which are spliced together at a genetic level during lymphocyte differentiation. Each individual has the capacity to manufacture an antibody which will combine with every possible antigen, but the body is only stimulated to manufacture a specific antibody after the introduction of the appropriate antigen. This may occur naturally by ingestion in the gut, by infection with bacteria or virus, or artificially during the process of immunization. Once an antibody has been made, an individual can produce relatively large quantities of it very easily. This is called the "memory" of the immune system. It was first recognized by the observation that infection with some diseases such as rubella may provide protection against subsequent re-infection.

When an antibody-antigen reaction has occurred several events may take place. First, the complex of antibody and antigen may form a molecular lattice which grows in size, and eventually such complexes will be removed from the blood by phagocytic cells. Second, the combination of such molecules can cause the activation of complement, a cascade of proteins present in inert form in blood which, when activated, may cause lysis of a cell. Alternatively the wandering macrophages of the reticulo-endothelial system may be directed to a specific site in the body and phagocytosis of foreign cells enhanced.

An essential principle of immunology is that each individual B-lymphocyte may produce many copies of only one specific immunoglobulin molecule directed against a single antigenic determinant (epitope). This is elegantly outlined in the clonal selection theory. This provides an explanation for features such as immunological memory, the distinction between self and non-self, immunological tolerance, and also auto-immune disease where the body's recognition of self and non-self may break down. The clonal selection theory states that on exposure to an antigen there is a proliferation in the clone of B-lymphocytes responsible for producing the antibody against that antigen. Once proliferation of a clone has occurred, then further exposure to the same antigen results in a rapid and large burst of antibody production accounting for the "memory" of the immune system. There are certain forbidden clones--those whose secreted antibody would be harmful to the host by interacting with normal human components. By constant immunological stimulation during infancy and childhood, a series of antibody-producing clones of B-cells arise which form the antibody repertoire of an individual. Clearly as every child's antigenic exposure is different in timing and quantity so the repertoire varies between individuals.