Antibody-antigen interactions

The interaction between antigens and antibodies is a reversible chemical reaction based on the summation of several noncovalent interactions. Multiple noncovalent bonds, comprising Van der Waals forces, hydrogen bonds and ionic bonds, are necessary in order to obtain a stable interaction, as each noncovalent bond is relative weak.

The combined strength of the noncovalent interactions between the antibody and the antigen is referred to as antibody affinity. Factors that may influence affinity include elements that are extrinsic to the antibody and antigens, such as:

temperature

pressure

ionic strength

the concentration of other macromolecules in the solution

Antibody affinity is not to be compared with antibody specificity, which enables antibodies to differentiate between antigenic determinants. When the antibody and the antigen approach each other, they are attracted by long-range forces, such as ionic bonds and hydrogen bonds. At close distance Van der Waals forces prevail and serve to pull the two complementary surfaces together. However, ionic bonds and hydrogen bonds still play a role at close distances, as ionic bonds between charged amino acid side-chains and hydrogen bonds bridging oxygen and/or nitrogen atoms strengthen the overall interaction. At close distance interactions occur between side-chains and the polypeptide backbone of the antibody and the respective antigen. No evidence is currently presented to show that each residue in the antigenic determinants interact with the antibody. In fact, it has been suggested that only a subset of contact residues within the antigen significantly contribute to the binding energy, referred to as hot spot residues. Thus, even though the interaction between antibodies and antigens is specific, even small changes may affect the strength of the antibody-antigen interaction. For example, loss of a single hydrogen bond at the interface can reduce the strength of interaction 1000-fold, as the overall interaction is a balance of many attractive and repulsive interactions. Moreover, substitution of single amino acids within the interface may have similar effect on reactivity, clearly illustrating the specificity of the interaction between antibodies and antigens. These effects of substitutions may arise from changes in the antibody sequence as well as in the antigen.