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.

Keywords: antibody; specificity; affinity; avidity; complementarity‐determining region

Figure 1. Structure of immunoglobulin G (IgG). (a) Schematic representation of a typical IgG. The L and H chains are shown in light orange and gray, respectively. Intermolecular disulfide bonds (S–S bonds) at the hinge region between two different heavy chains (green) or between the heavy and the light chains (magenta) are shown. (b) Three‐dimensional structure of murine IgG (PDB entry 1igy) (Harris et al., ). The residues in green correspond to S–S bonds at the hinge region. The attached carbohydrates in the Fc fragment are shown as sticks. The figure was prepared with CHIMERA.
Figure 2. The immunoglobulin fold. The variable domain of a heavy chain is shown. The stabilising intramolecular S–S bond between two Cys residues is shown with sticks. The figure was prepared with CHIMERA.
Figure 3. Structure of complementarity‐determining regions (CDRs). (a) Variable domains of a murine immunoglobulin G (composed of heavy chain and light chain) are shown (PDB entry 2e27) (Tsumoto et al., ). The hypervariable regions, CDRs comprising the antigen‐binding site, are depicted in red, green, and magenta. These are located at the one edge of the β‐barrel structure. The antigen (hapten) is shown with sticks. (b) Fab fragment of 10C9 complexed with the antigen 10C9‐ABCDE (PDB entry 2Z92) (Ui et al., ) showing the location of water molecules (red spheres). The figure was prepared with CHIMERA.
Figure 4. Molecular basis for antibody diversity. The figure illustrates an example for the heavy chain. In the human genome, one of the about 80 VH genes (in mouse, about 100) recombines with one of the 30 D segments (in mouse, about 10), and one of the 6 JH segments (in mouse, 4), producing the functional V–D–J gene in an immune B cell. The recombined DNA (deoxyribonucleic acid) is transcribed, spliced and translated into a polypeptide chain. Half of the VH genes in human B cell seem to be pseudo‐genes.
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Further Reading

Branden C and Branden J (1999) Introduction to Protein Structure, 2nd edn. New York: Garland Publishing.

Delves P, Martin S, Burton D and Roitt I (2007) Essential Immunology, 11th edn. London: John Wiley & Sons, Ltd.

Paul WE (2013) Fundamental Immunology, 7th edn. Philadelphia: Lippincott Williams & Wilkins.

Roitt I, Brostoff J and Male D (1996) Immunology, 3rd edn. London: Mosby Year Book.

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How to Cite close
Tsumoto, Kouhei, and Caaveiro, Jose MM(Dec 2016) Antigen–Antibody Binding. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001117.pub3]