Antigen-antibody interaction

Antigen-antibody interaction, or antigen-antibody reaction, is a specific chemical interaction between antibodies produced by B cells of the white blood cells and antigens during immune reaction. It is the fundamental reaction in the body by which the body is protected from complex foreign molecules, such as pathogens and their chemical toxins. In the blood, the antigens are specifically and with high affinity bound by antibodies to form an antigen-antibody complex. The immune complex is then transported to cellular systems where it can be destroyed or deactivated.

The first correct description of the antigen-antibody reaction was given by Richard J. Goldberg at the University of Wisconsin in 1952.[1][2] It came to be known as "Goldberg's theory" (of antigen-antibody reaction).[3]

There are several types of antibodies and antigens, and each antibody is capable of binding only to a specific antigen. The specificity of the binding is due to specific chemical constitution of each antibody. The antigenic determinant or epitope is recognized by the paratope of the antibody, situated at the variable region of the polypeptide chain. The variable region in turn has hyper-variable regions which are unique amino acid sequences in each antibody. Antigens are bound to antibodies through weak and noncovalent interactions such as electrostatic interactions, hydrogen bonds, Van der Waals forces, and hydrophobic interactions.[4]

The principles of specificity and cross-reactivity of the antigen-antibody interaction are useful in clinical laboratory for diagnositic purposes. One basic application is determination of ABO blood group. It is also used as a molecular technique for infection with different pathogens, such as HIV, microbes, and helminth parasites.

Antibody structure

In an antibody, the Fab (fragment, antigen-binding) region is formed from the amino-terminal end of both the light and heavy chains of the immunoglobulin polypeptide. This region called V (variable) domain is composed of amino acid sequences that define each type of antibody and their binding affinity to an antigen. The combined sequence of variable light chain (VL) and variable heavy chain (VH) creates three hypervariable regions (HV1, HV2, and HV3). In VL these are roughly from residues 28 to 35, from 49 to 59, and from 92 to 103, respectively. HV3 is the most variable part. Thus these regions are the paratope, the binding site of antigen. The rest of the V region between the hypervariable regions are called framework regions. Each V domain has four framework domains, namely FR1, FR2, FR3, and FR4.[4][5]

Properties

Chemical basis of antigen-antibody interaction

Antibodies bind antigens through weak chemical interactions, and bonding is essentially non-covalent. Electrostatic interactions, hydrogen bonds, van der Waals forces, and hydrophobic interactions are all known to be involved depending on the interaction sites.[6][7]

Affinity of the interaction

Antigen and antibody interact through a high affinity binding much like lock and key.[8] A dynamic equilibrium exists for the binding. For example, the reaction is a reversible one, and can be expressed as:

where [Ab] is the antibody concentration and [Ag] is the antigen concentration, either in free ([Ab],[Ag]) or bound ([AbAg]) state.

The equilibrium association constant can therefore be represented as:

where K is the equilibrium constant.

Reciprocally the dissociation constant will be:

However, these equations are applicable only to a single epitope binding, i.e. one antigen on one antibody. Since the antibody necessarily has two paratopes, and in many circumstances complex binding occurs, the multiple binding equilibrium can be summed up as:

= r/c(n-r)

where, at equilibrium, c is the concentration of free ligand, r represents the ratio of the concentration of bound ligand to total antibody concentration and n is the maximum number of binding sites per antibody molecule (the antibody valence).

The overall strength of the binding of an antibody to an antigen is termed its avidity for that antigen. Since antibodies are bivalent or polyvalent, this is the sum of the strengths of individual antibody-antigen interactions. The strength of an individual interaction between a single binding site on an antibody and its target epitope is termed the affinity of that interaction.

Avidity and affinity can be judged by the dissociation constant for the interactions they describe. The lower the dissociation constant, the higher the avidity or affinity, and the stronger the interaction.

Application

Antigen-antibody interaction is used in laboratory techniques for serological test of blood compatibility and various pathogenic infections. The most basic is ABO blood group determination, which is useful for blood transfusion.[9] Sophisticated applications include ELISA,[10] enzyme-linked immunospot (Elispot), immunofluorescence, and immunoelectrophoresis.[11][12][13]

References

  1. ↑ Goldberg, Richard J. (1952). "A Theory of Antibody—Antigen Reactions. I. Theory for Reactions of Multivalent Antigen with Bivalent and Univalent Antibody". Journal of the American Chemical Society. 74 (22): 5715–5725. doi:10.1021/ja01142a045.
  2. ↑ Sahimi, Muhammad (1994). Applications of Percolation Theory. London: CRC Press. p. 257. ISBN 978-0-203-22153-2.
  3. ↑ Spiers, JA (1958). "Goldberg's theory of antigen-antibody reactions in vitro". Immunology. 1 (2): 89–102. PMC 1423897 Freely accessible. PMID 13538526.
  4. 1 2 Janeway, Charles A Jr; Travers, Paul; Walport, Mark; Shlomchik, Mark J (2001). Immunobiology: The Immune System in Health and Disease (5 ed.). New York: Garland Science. ISBN 0-8153-3642-X.
  5. ↑ Mian, I.Saira; Bradwell, Arthur R.; Olson, Arthur J. (1991). "Structure, function and properties of antibody binding sites". Journal of Molecular Biology. 217 (1): 133–151. PMID 1988675. doi:10.1016/0022-2836(91)90617-F.
  6. ↑ van Oss, CJ; Good, RJ; Chaudhury, MK (1986). "Nature of the antigen-antibody interaction. Primary and secondary bonds: optimal conditions for association and dissociation". Journal of Chromatography. 376: 111–9. PMID 3711190.
  7. ↑ Absolom, DR; van Oss, CJ (1986). "The nature of the antigen-antibody bond and the factors affecting its association and dissociation". CRC Critical Reviews in Immunology. 6 (1): 1–46. PMID 3522103.
  8. ↑ Braden, BC; Dall'Acqua, W; Eisenstein, E; Fields, BA; Goldbaum, FA; Malchiodi, EL; Mariuzza, RA; Schwarz, FP; Ysern, X; Poljak, RJ (1995). "Protein motion and lock and key complementarity in antigen-antibody reactions.". Pharmaceutica acta Helvetiae. 69 (4): 225–30. PMID 7651966. doi:10.1016/0031-6865(94)00046-x.
  9. ↑ Mayer, Gene. "Immunoglobulins- antigen-antibody reactions and selected tests". Microbiology and Immunology. University of South Carolina School of Medicine. Retrieved 10 March 2015.
  10. ↑ Margolis, Simeon (5 January 2012). "Antigen/Antibody Tests for Infectious Disease". Remedy Health Media, LLC. Retrieved 10 March 2015.
  11. ↑ Taylor, Charles W.; Chakrabarty, Subhas; Schauder, Keith S.; Yeoman, Lynn C. (1983). "Identification of Cytosolic Antigens from GW-39 Adenocarcinoma Cells by Crossed Immunoelectrophoresis and Immunofluorescence". Immunological Investigations. 12 (3): 315–329. doi:10.3109/08820138309050753.
  12. ↑ Ferenčík, Miroslav (2013). Handbook of Immunochemistry. Netherlands: Springer. pp. 309–386. ISBN 978-94-010-4678-7. doi:10.1007/978-94-011-1552-0_12.
  13. ↑ Odell, Ian D; Cook, Deborah (2013). "Immunofluorescence Techniques". Journal of Investigative Dermatology. 133 (1): e4. doi:10.1038/jid.2012.455.
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