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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. A particular important aspect relates to the phenomenon of ′avidity entropy′.^[1] 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.^{[citation needed]}

Antibody-antigen interaction

Avidity is commonly applied to antibody interactions in which multiple antigen-binding sites simultaneously interact with the target antigenic epitopes, often 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.^{[citation needed]}

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.^[2] 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.^{[citation needed]}

Affinity

Binding affinity is a measure of dynamic equilibrium of the ratio of on-rate (k_on) and off-rate (k_off) under specific concentrations of reactants. The affinity constant, K_a, is the inverse of the dissociation constant, 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.^{[citation needed]}

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.^{[citation needed]} 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.^[3]

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 (or equilibrium constant): $K_{a}={\frac {k_{on}}{k_{off}}}={\frac {[AbAg]}{[Ab][Ag]}}$

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

Application

The 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 a 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.^[4]

External links

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

A number of technologies exist to characterise the avidity of molecular interactions including switchSENSE and surface plasmon resonance.^[5]^[6]

References

^ Kitov PI, Bundle DR (2003). "On the nature of the multivalency effect: a thermodynamic model". Journal of the American Chemical Society. 125 (52): 16271–84. doi:10.1021/ja038223n. PMID 14692768.
^ Rudnick SI, Adams GP (2009). "Affinity and avidity in antibody-based tumor targeting". Cancer Biotherapy & Radiopharmaceuticals. 24 (2): 155–61. doi:10.1089/cbr.2009.0627. PMC 2902227. PMID 19409036.
^ Janeway, Charles A; Travers, Paul; Walport, Mark; Shlomchik, Mark J (2001). Immunobiology (5th ed.). New York: Garland Science. ISBN 0-8153-3642-X.^{[page needed]}
^ Curdt I, Praast G, Sickinger E, Schultess J, Herold I, Braun HB, Bernhardt S, Maine GT, Smith DD, Hsu S, Christ HM, Pucci D, Hausmann M, Herzogenrath J (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". Journal of Clinical Microbiology. 47 (3): 603–13. doi:10.1128/JCM.01076-08. PMC 2650902. PMID 19129411.
^ Gjelstrup LC, Kaspersen JD, Behrens MA, Pedersen JS, Thiel S, Kingshott P, Oliveira CL, Thielens NM, Vorup-Jensen T (2012). "The role of nanometer-scaled ligand patterns in polyvalent binding by large mannan-binding lectin oligomers". Journal of Immunology. 188 (3): 1292–306. doi:10.4049/jimmunol.1103012. PMID 22219330.
^ Vorup-Jensen T (2012). "On the roles of polyvalent binding in immune recognition: perspectives in the nanoscience of immunology and the immune response to nanomedicines". Advanced Drug Delivery Reviews. 64 (15): 1759–81. doi:10.1016/j.addr.2012.06.003. PMID 22705545.

@@ Line 1: / Line 1: @@
-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. A particular important aspect relates to the phenomenon of ′avidity entropy′.<ref>{{cite journal |vauthors=Kitov PI, Bundle DR |title=On the nature of the multivalency effect: a thermodynamic model |journal=Journal of the American Chemical Society |volume=125 |issue=52 |pages=16271–84 |year=2003 |pmid=14692768 |doi=10.1021/ja038223n }}</ref> 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]].{{fact}}
+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. A particular important aspect relates to the phenomenon of ′avidity entropy′.<ref>{{cite journal |vauthors=Kitov PI, Bundle DR |title=On the nature of the multivalency effect: a thermodynamic model |journal=Journal of the American Chemical Society |volume=125 |issue=52 |pages=16271–84 |year=2003 |pmid=14692768 |doi=10.1021/ja038223n }}</ref> 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]].{{fact|date=January 2016}}
 ==Antibody-antigen interaction==
-Avidity is commonly applied to [[antibody]] interactions in which multiple antigen-binding sites simultaneously interact with the target [[antigen]]ic [[epitope]]s, often 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.{{fact}}
+Avidity is commonly applied to [[antibody]] interactions in which multiple antigen-binding sites simultaneously interact with the target [[antigen]]ic [[epitope]]s, often 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.{{fact|date=January 2016}}
-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.<ref name="pmid19409036">{{cite journal |vauthors=Rudnick SI, Adams GP |title=Affinity and avidity in antibody-based tumor targeting |journal=Cancer Biotherapy & Radiopharmaceuticals |volume=24 |issue=2 |pages=155–61 |year=2009 |pmid=19409036 |pmc=2902227 |doi=10.1089/cbr.2009.0627 }}</ref> 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.{{fact}}
+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.<ref name="pmid19409036">{{cite journal |vauthors=Rudnick SI, Adams GP |title=Affinity and avidity in antibody-based tumor targeting |journal=Cancer Biotherapy & Radiopharmaceuticals |volume=24 |issue=2 |pages=155–61 |year=2009 |pmid=19409036 |pmc=2902227 |doi=10.1089/cbr.2009.0627 }}</ref> 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.{{fact|date=January 2016}}
 ===Affinity===
-Binding affinity is a measure of dynamic equilibrium of the ratio of on-rate (k<sub>on</sub>) and off-rate (k<sub>off</sub>) under specific concentrations of reactants. The affinity constant, [[Equilibrium_constant|K<sub>a</sub>]], is the inverse of the dissociation constant, [[Dissociation_constant|K<sub>d</sub>]]. The strength of complex formation in solution is related to the [[stability constants of complexes]], however in case of large biomolecules, such as [[Receptor (biochemistry)|receptor]]-[[Ligand (biochemistry)|ligand]] pairs, their interaction is also dependent on other structural and thermodynamic properties of reactants plus their orientation and immobilization.{{fact}}
+Binding affinity is a measure of dynamic equilibrium of the ratio of on-rate (k<sub>on</sub>) and off-rate (k<sub>off</sub>) under specific concentrations of reactants. The affinity constant, [[Equilibrium_constant|K<sub>a</sub>]], is the inverse of the dissociation constant, [[Dissociation_constant|K<sub>d</sub>]]. The strength of complex formation in solution is related to the [[stability constants of complexes]], however in case of large biomolecules, such as [[Receptor (biochemistry)|receptor]]-[[Ligand (biochemistry)|ligand]] pairs, their interaction is also dependent on other structural and thermodynamic properties of reactants plus their orientation and immobilization.{{fact|date=January 2016}}
-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]].{{fact}} 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 bond]]s, [[ionic bond|electrostatic bond]]s, [[van der Waals force]]s and [[hydrophobic effect|hydrophobic force]]s.<ref>{{cite book |first1=Charles A |last1=Janeway |first2=Paul |last2=Travers |first3=Mark |last3=Walport |first4=Mark J |last4=Shlomchik |year=2001 |title=Immunobiology |edition=5th |url=http://www.ncbi.nlm.nih.gov/books/NBK10757/ |location=New York |publisher=Garland Science |isbn=0-8153-3642-X }}{{pn}}</ref>
+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]].{{fact|date=January 2016}} 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 bond]]s, [[ionic bond|electrostatic bond]]s, [[van der Waals force]]s and [[hydrophobic effect|hydrophobic force]]s.<ref>{{cite book |first1=Charles A |last1=Janeway |first2=Paul |last2=Travers |first3=Mark |last3=Walport |first4=Mark J |last4=Shlomchik |year=2001 |title=Immunobiology |edition=5th |url=http://www.ncbi.nlm.nih.gov/books/NBK10757/ |location=New York |publisher=Garland Science |isbn=0-8153-3642-X }}{{pn|date=January 2016}}</ref>
 Calculation of binding affinity for bimolecular reaction (1 antibody binding site per 1 antigen):