Antigen–Antibody Binding

Izumi Kumagai, Tohoku University, Sendai, Japan
Kouhei Tsumoto, The University of Tokyo, Tokyo, Japan

Published online: April 2010

DOI: 10.1002/9780470015902.a0001117.pub2

Full Article on Wiley Online Library

Antibodies are a family of glycoproteins that bind specifically to foreign molecules (antigens). The antibody-binding sites are formed by six segments of variable structure (CDRs) supported by a scaffolding of essentially invariant architecture (framework regions). Shape complementarity of binding surfaces (in the case of protein antigens) or close contact with small antigens (hapten, peptide or others), with some complementation of water molecules, is important. 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 contancts and buried surfaces on complexation correlates well with the affinity, and hydrogen-bond formation is in principle critical for high specificity and affinity of an antibody for the target. Antibodies have at least two antigen-binding sites, which increase the apparent affinity, called avidity, of antibodies for the targets.

Key Concepts:

The binding between antibodies and antigens has high specificity and affinity resulting from various structural and energetic aspects. Multivalency of antibodies is important to understand the interaction of an antibody with its antigen.

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 as solid lines, with the intramolecular disulfide linking Cys residues (S–S), that are characteristic of each immunoglobulin domain as shown in Figure 2. (b) Three-dimensional structure of IgG. The drawing is a crystal structure of murine IgG (PDB entry 1igy). Some residues shown as CPK were S–S bonds within the hinge region, and attached carbohydrates are shown as sticks. Drawn using RasMol.
	Figure 2. The immunoglobulin fold. The variable domain of a light chain is shown. Drawn using MOLSCRIPT.
	Figure 3. Structure of complementarity-determining regions (CDRs). (a) Variable domains of a murine IgG (composed of heavy- and light chain) are shown (from 10C9 JBC (2008)). The hypervariable regions, CDRs comprising the antigen-binding site are shown by colour lines. These are located at the one edge of the barrel structure. (b) Fab fragment of 10C9 complexed with the antigen 10C9-ABCDE (Tsumoto, JBC 2008). Drawn using RasMol.
	Figure 4. Molecular basis for antibody diversity. Only the case of heavy chain has been shown. In the human genome, one of the approximately 80 VH genes (in mouse, approximately 100) recombines with one of the 30 D segments (in mouse, approximately 10), and one of the 6 J segments (in mouse, 4) producing a functional V-D-J gene in the B cell. The recombined DNA is transcribed, spliced and translated into a polypeptide chain. Half of the VH genes in human B cell seem to be pseudogenes.

Further Reading
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	Bhat TN, Mariuzza RA, Poljak RJ et al. (1994) Bound water molecules and conformational stabilization help mediate an antigen–antibody association. Proceedings of the National Academy of Sciences of the USA 91: 1089–1093.
	Bostrom J, Yu SF, Kan D et al. (2009) Variants of the antibody herceptin that interact with HER2 and VEGF at the antigen binding site. Science 323: 1610–1614.
	book Branden C and Tooze J (eds) (1999) “Introduction to protein structure, chap. 15” Recognition of Foreign Molecules by the Immune System. New York: Garland Publishing.
	Chitarra V, Alzari PM, Poljak RJ et al. (1993) Three-dimensional structure of a heteroclitic antigen–antibody cross-reaction complex. Proceedings of the National Academy of Sciences of the USA 90: 7711–7715.
	Chothia C, Lesk AM, Tramontano A et al. (1989) Conformations of immunoglobulin hypervariable regions. Nature 342: 877–883.
	Davies DR and Cohen GH (1996) Interactions of protein antigens with antibodies. Proceedings of the National Academy of Sciences of the USA 93: 7–12.
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	Mariuzza RA (2006) Multiple paths to multispecificity. Immunity 24: 359–368.
	Padlan EA (1994) Anatomy of the antibody molecule. Molecular Immunology 31: 169–217.
	book Peter D, Seamus M, Dennis B and Ivan R (2007) “Essential immunology, 11th edn. chaps. 3 and 5” Antibodies, The Primary Recognition with Antigen. New York: Wiley.
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Article Title:	Antigen–Antibody Binding
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Antigen–Antibody Binding

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