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In the context of biochemistry, avidity refers to the accumulated strength of multiple affinities of individual non-covalent binding interactions, such as between a protein receptor and its ligand, and is commonly referred to as functional affinity. As such, avidity is distinct from affinity, which describes the strength of a single interaction. However, because individual binding events increase the likelihood of other interactions to occur (i.e. increase the local concentration of each binding partner in proximity to the binding site), avidity should not be thought of as the mere sum of its constituent affinities but as the combined effect of all affinities participating in the biomolecular interaction. Biomolecules often form heterogenous complexes or homogenous oligomers and multimers or polymers. If clustered proteins form an organized matrix, such as the clathrin-coat, the interaction is a described as matricity.

Antibody-antigen interaction

Avidity is commonly applied to antibody interactions in which multiple antigen-binding sites simultaneously interact with the target antigenic epitopes, otfen in multimerized structures. Individually, each binding interaction may be readily broken, however, when many binding interactions are present at the same time, transient unbinding of a single site does not allow the molecule to diffuse away, and binding of that weak interaction is likely to be restored.

Each antibody has at least two antigen-binding sites, therefore antibodies are bivalent to multivalent. Avidity (functional affinity) is the accumulated strength of multiple affinities.^[1] For example IgM is said to have low affinity but high avidity because it has 10 weak binding sites for antigen as opposed to the 2 stronger binding sites of IgG, IgE and IgD with higher single binding affinities.

Affinity

Binding affinity is a measure of dynamic equilibrium between the reciprocal on-rate (k_on, calculated from K_a) and off-rate (k_off, calculated from K_d) under specific concentrations of reactants in solution. There is always an inverse relationship between affinity and K_d. The strength of complex formation in solution is related to the stability constants of complexes, however in case of large biomolecules, such as receptor-ligand pairs, their interaction is also dependent on other structural and thermodynamic properties of reactants plus their orientation and immobilization.

There are multiple methods to investigate protein–protein interactions existing with differences in immobilization of each reactant in 2D or 3D orientation. The measured affinities are stored in public databases, such as the Ki Database and BindingDB. As an example, affinity is the binding strength between the complex structures of the epitope of antigenic determinant and paratope of antigen-binding site of an antibody. Participating non-covalent interactions may include hydrogen bonds, electrostatic bonds, van der Waals forces and hydrophobic forces.^[2]

Calculation of binding affinity for bimolecular reaction (1 antibody binding site per 1 antigen):

$[Ab]+[Ag]\leftrightharpoons [AbAg]$

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

calculation of association constant: $K_{a}={\frac {k_{on}}{k_{off}}}={\frac {[AbAg]}{[Ab][Ag]}}$

calculation of dissociation constant: $K_{d}={\frac {k_{off}}{k_{on}}}={\frac {[Ab][Ag]}{[AbAg]}}$

where ratio of k_a and k_d describes the binding affinity:

$K={\frac {K_{a}}{K_{d}}}={\frac {[AbAg]}{[Ab][Ag]}}$

where K is the equilibrium constant.

Application

Avidity test for rubella virus, Toxoplasma gondii, cytomegalovirus (CMV), varicella-zoster virus, human immunodeficiency virus (HIV), hepatitis viruses, Epstein-Barr virus, and others was developed few years ago. This test helps us to distinguish acute, recurrent or past infection by avidity of marker-specific IgG. Currently there are two avidity assay in use. These are well known chaotropic (conventional) assay and recently developed AVIcomp (avidity competition) assay.^[3]

External links

Antibody+Avidity at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

References

Roitt, Ivan, et al., Immunology, 6th edn, 2001, Mosby Publishers, page 72.

^ Rudnick SI, Adams GP (2009). "Affinity and avidity in antibody-based tumor targeting". Cancer Biother Radiopharm. 24 (2): 155–61. doi:10.1089/cbr.2009.0627. PMC 2902227. PMID 19409036.
^ Janeway CA Jr, Travers P, Walport M, et al. Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Science; 2001. Available from: http://www.ncbi.nlm.nih.gov/books/NBK10757/
^ Curdt I, Praast G, Sickinger E, Schultess J, Herold I, Braun HB; et al. (2009). "Development of fully automated determination of marker-specific immunoglobulin G (IgG) avidity based on the avidity competition assay format: application for Abbott Architect cytomegalovirus and Toxo IgG Avidity assays". J Clin Microbiol. 47 (3): 603–13. doi:10.1128/JCM.01076-08. PMC 2650902. PMID 19129411. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)

Micro Class at SIUE

[pmid19409036-1] Rudnick SI, Adams GP (2009). "Affinity and avidity in antibody-based tumor targeting". Cancer Biother Radiopharm. 24 (2): 155–61. doi:10.1089/cbr.2009.0627. PMC 2902227. PMID 19409036.

[2] Janeway CA Jr, Travers P, Walport M, et al. Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Science; 2001. Available from: http://www.ncbi.nlm.nih.gov/books/NBK10757/

[pmid19129411-3] Curdt I, Praast G, Sickinger E, Schultess J, Herold I, Braun HB; et al. (2009). "Development of fully automated determination of marker-specific immunoglobulin G (IgG) avidity based on the avidity competition assay format: application for Abbott Architect cytomegalovirus and Toxo IgG Avidity assays". J Clin Microbiol. 47 (3): 603–13. doi:10.1128/JCM.01076-08. PMC 2650902. PMID 19129411. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)

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-In [[protein]]s, '''avidity''' refers to the accumulated strength of ''multiple'' affinities of individual [[non-covalent]] binding interactions and is commonly referred to as functional affinity. As such, avidity is distinct from [[chemical affinity|affinity]], which describes the strength of a ''single'' interaction. However, because individual binding events increase the likelihood of other interactions to occur (i.e. increase the local concentration of each binding partner in proximity to the binding site), avidity should not be thought of as the mere sum of its constituent affinities but as the combined effect of all affinities participating in the biomolecular interaction.
+In the context of biochemistry, '''avidity''' refers to the accumulated strength of ''multiple'' affinities of individual [[non-covalent]] binding interactions, such as between a protein receptor and its ligand, and is commonly referred to as functional affinity. As such, avidity is distinct from [[chemical affinity|affinity]], which describes the strength of a ''single'' interaction. However, because individual binding events increase the likelihood of other interactions to occur (i.e. increase the local concentration of each binding partner in proximity to the binding site), avidity should not be thought of as the mere sum of its constituent affinities but as the combined effect of all affinities participating in the biomolecular interaction.
 Biomolecules often form heterogenous complexes or homogenous [[oligomer]]s and multimers or [[polymer]]s.
 If clustered proteins form an organized matrix, such as the [[clathrin]]-coat, the interaction is a described as [[matricity]].