Antigen–Antibody Binding

Abstract Antibodies are a family of glycoproteins that bind specifically to target molecules (antigens). The antibody‐binding sites are formed by six segments of variable structure (CDRs) supported by a scaffold of essentially invariant architecture (framework regions). Shape complementarity between the contact surfaces (in the case of protein antigens) or close interactions with small antigens (hapten, peptide or others), together with complementation of water molecules, are important to achieve high affinity and specificity. The binding of an antigen to an antibody takes place by the formation of multiple noncovalent bonds between the antigen and the amino acids of the binding site. The increase in van der Waals contacts and/or buried surfaces upon complexation generally correlates well with the binding strength. Hydrogen bonds are in most cases critical to achieve high specificity and affinity for the antigen target. Importantly, antibodies have at least two antigen binding sites, boosting the effective affinity of the antibody for its target by a mechanism termed avidity. Key Concepts The binding between antibodies and antigens is characterised by high specificity and affinity resulting from distinct structural and energetic features. Non‐covalent forces dominate antibody‐antigen interactions. Generally, the recognition of an antigen is driven by the favorable change of enthalpy, and opposed by the entropy term. Multivalency is an important property of antibodies that govern their interaction with antigens in a biological setting. Progress in the fundamental understanding of antigen‐antibody interactions will lead to the rational design of more efficient and potent therapeutic antibodies.