Antigens multivalent

Secondary antibody-antigen reactions occur as a result of antigen multivalency, and result in agglutination or precipitation of a polymeric antigen-antibody network. A visible product is formed over a time scale of minutes to hours (Eq. 5.2) ... 

The definition of an association constant for an antibody—antigen reaction can become more complex if the antibody—antigen reaction iavolves a multivalent antigen, as is the case when a polyclonal antisemm is used for detection of an antigen. This type of multivalent binding is termed avidity and is defined by the equation ... 

Definition of the association (or avidity) constant for such multivalent antibody—antigen reactions must consider not only the heterogeneity of the antibodies and the antigen determinant site(s), but also an apparent additive effect of binding two antigen molecules to a single antibody. Such effects lead... 

Here, we describe the design and preparation of antibody supramolecular complexes and their application to a highly sensitive detection method. The complex formation between antibodies (IgG) and multivalent antigens is investigated. When an antibody solution is mixed with divalent antigen, a linear or cyclic supramolecule forms [26-29]. With trivalent antigens, the antibody forms network structures. These supramolecular formations are utilized for the ampH-fication of detection signals on the biosensor techniques. 

Fig. 3. Haptens and multivalent antigens prepared in this syudy. The viologen derivative, 4,4 -bipyridinium, l-(carboxypentyl)-l -methyl-dichloride (1), divalent antigen 2, and trivalent antigen 3. Anti-porphyrin antibodies were elicited for [5-(4-carboxyphenyl)-10,15,20-tris-(4-methylpyridyl)]porphine (3MPylC) or meso-tetrakis(4-carboxyphenyl)porphine (TCPP). meso-Tetrakis(4-methylpyridyl)porphine (TMPyP) was used to investigate the specificity of the antibody dendrimer for porphyrins...

Antibody molecules are bivalent whilst antigens can be multivalent. The resultant combination may result in either small, soluble complexes, or large insoluble aggre tes, depending on the nature of the two molecules in the system. The following are examples of the reactions that can occur. 

Hlavacek WS, Percus JK, Percus OE et al (2002) Retention of antigen on follicular dendritic cells and Blymphocytes through complement-mediated multivalent ligand-receptor interactions theory and application to HIV treatment. Math Biosci 176 185-202... 

Liposome conjugates may be used in various immunoassay procedures. The lipid vesicle can provide a multivalent surface to accommodate numerous antigen-antibody interactions and thus increase the sensitivity of an assay. At the same time, it can function as a vessel to carry encapsulated detection components needed for the assay system. This type of enzyme-linked immunosorbent assay (ELISA) is called a liposome immunosorbent assay or LISA. One method of using liposomes in an immunoassay is to modify the surface so that it can interact to form biotin-avidin or biotin-streptavidin complexes. The avidin-biotin interaction can be used to increase detectability or sensitivity in immunoassay tests (Chapter 23) (Savage et al., 1992). 

Plotz, P.H., and Rifai, A. (1982) Stable, soluble, model immune complexes made with a versatile multivalent affinity-labeling antigen. Biochemistry 21, 301. 

In addition to this, virus-like particles have been generated that contain a form of HBsAg that has been modified at the N-terminus so that it can be utilized to present T- and B-cell epitopes. The fact that the VLPs remained intact suggests that this alteration did not negatively affect the antigenic properties of the protein and that a multivalent response could be made possible. 

Unless all these factors are taken into account, it is usually more appropriate to refer to the results of a flow cytometric analysis in terms of antibodies bound per cell rather than antigens per cell. Stoichiometry will be even less certain with multivalent IgM antibodies the usually low monovalent affinity and strong role of avidity in the binding of IgM antibodies make them of limited value for antigen quantitation. Theoretically, the most precise alternative would be the use of directly labeled monovalent antibody fragments, which would avoid problems of variable stoichiometry. However, in addition to the inconvenience of producing suitable labeled monovalent antibody fragments, the increased off rate of monovalently bound antibody may make analysis more difficult. 

Depending on the particular vector system used, gp3 fusions can be displayed either multivalently for selection by avidity or monovalently to select for binders with the highest affinity. By fusing VH or VL antigen binding domains (Fv) or VH-CH and VL-CL (Fabs) to a bacterial leader sequence, the Ab chains are directed through the cytoplasmic membrane into the gap between... 

The multivalency of peptide dendrimers has also been used to increase the binding avidity of antigens to antibodies in various immunological assays and diagnostic tests. 27,43,47,48,55-59 Examples in the literature have been reported where the MAP format increases the binding avidity and sensitivity, in some cases >100000 fold. In addition to immunology, MAP types of dendrimers have found applications in areas such as inhibitors, 44,45,51,60,61 artificial proteins, 62 affinity purification, 63 and intracellular transportation, 41 as well as in drug discovery. 53 ... 

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