Antibody-Antigen Interactions

An antigen is usually defined as a substance that causes an immune response when introduced into an organism and is capable of binding with the specific antibodies. This binding is mediated by the sum of many weak interactions between the antigen and antibody. These weak interactions include hydrogen bonds, van der Waals forces, and ionic and/or hydrophobic interactions.

These interactions can only take place if the antigen and antibody molecules are close enough for some of the individual atoms to fit into complementary recesses. The complementary regions of an antibody are its 2 antigen binding sites (thus the antibody is said to be bivalent). The corresponding region(s) of the antigen is referred to as an antigenic determinant. Most antigens have multiple determinants; if 2 or more are identical, the antigen is said to be multivalent.

As the binding of an antibody (ab) to its antigen (ag) is reversible, the binding reaction can be expressed as:

The strength of the interaction is expressed as the affinity constant K_a, where:

In this equation, [ab:ag] is the molar concentration of the antibody-antigen complex, and [ab] and [ag] are the molar concentrations of the antibody and antigen, respectively. Affinity constants can vary widely between different antibodies and antigens, and are affected by pH, temperature, and solvent.

The affinity of an antibody reflects how well the antigenic determinant fits in the antigen binding site of antibody and is independent of the number of binding sites. Another way to measure the antibody-antigen interaction is the avidity of the binding, which reflects the overall stability of the antibody-antigen complex. Avidity is defined as the total binding strength of all of its binding sites together. Thus, it is influenced by the affinity of the antibody for its antigen and the valencies of both the antibody and the antigen. A typical IgG molecule will bind up to 10,000 times more strongly to a multivalent antigen if both antigen-binding sites are engaged than if only one site binds the antigen.

The multivalent nature of most antibodies and antigens often causes secondary reactions such as precipitation, cell clumping, and complement fixation in an organism. In the laboratory, we can make use of these sorts of reactions in techniques such as western blotting, ELISAs, and immunoprecipitation.

A more detailed description of how antibodies interact with certain antigens can be found in: Davies DR and Cohen GH. (2004). Interactions of protein antigens with antibodies. Proc. Natl. Acad. Sci. USA 93:7-12.