Antibody bivalent

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. 

Hollinger, P., Prospero, T., and Winter, G. (1993). "Diahodies" Small bivalent and bispecific antibody fragments. Proc. Natl. Acad. Sci. USA 90, 6444-6448. 

Figure 20.10 Digestion of IgG class antibodies with pepsin results in heavy chain cleavage below the disulfide groups in the hinge region. The bivalent fragments that are formed are called F(ab )2. The remaining Fc region normally is severely degraded into smaller peptide fragments.

The fluidity of lipid bilayers permits dynamic interactions among membrane proteins. For example, the interactions of a neurotransmitter or hormone with its receptor can dissociate a transducer protein, which in turn will diffuse to interact with other effector proteins (Ch. 19). A given effector protein, such as adenylyl cyclase, may respond differently to different receptors because of mediation by different transducers. These dynamic interactions require rapid protein diffusion within the plane of the membrane bilayer. Receptor occupation can initiate extensive redistribution of membrane proteins, as exemplified by the clustering of membrane antigens consequent to binding bivalent antibodies [8]. In contrast to these examples of lateral mobility, the surface distribution of integral membrane proteins can be fixed by interactions with other proteins. Membranes may also be partitioned into local spatial domains consisting of networks... 

Antibodies Affinity labeling of antibody combining sites as illustrated by anti-dinitrophenyl antibodies, 46, 479 p-azoben-zenearsonate antibody, 46, 492 affinity cross-linking of heavy and light chains, 46, 501 bivalent affinity labeling haptens in the formation of model immune complexes, 46, 505 DNP-based diazoketones and azides, 46, 508 labeling of antilactose antibody, 46, 516. 

The polyvalency of IgM causes it to bind more firmly to an antigen than either a univalent or bivalent antibody. In this respect, a single molecule of IgM can cause lysis of a cell. Furthermore, the joining chain (J) has been detected in polymeric IgM and IgA, but not in the other immunoglobulins. About 10% of the IgM in external secretions has the secretory component attached. One wonders whether these characteristics of the IglNI are responsible for its take-over role in the gut, when there is a defective synthesis of IgA as in celiac or in Crohn s disease or in ulcerative colitis. 

Hewat, E. A. and Blaas, D. (1996). Structure of a neutralizing antibody bound bivalently to human rhinovirus 2. EMBO]. 15,1515-1523. 

M Mammen, FA Gomez, GM Whitesides. Determination of the binding of ligands containing the lV-2,4-dinitrophenyl group to bivalent monoclonal rat antibody using affinity capillary electrophoresis. Anal Chem 67 3526—3535, 1995. 

Figure 26-13 Synaptonemal complexes. (A) Aligned pairs of homologous chromatids lying 0.4 pm apart in Allium cepa. Arrows indicate "recombination nodules" which may be involved in initiating formation of crossovers. Portions of meiotic chromosomes of lily are shown at successive stages (B) Pachytene. (C) Portion of diplotene nucleus. (D) A bivalent at diplo-tene. (E) Two bivalents at diakinesis. Pairs of sister chromatids are coiled with appropriate handedness. (F) Sister chromatid cores are far apart in preparation for separation. A chiasma is present between the two central strands. (B) through (F) courtesy of Stephen Stack.279,279d (G) Pair of sister chromatids coiled with opposite handedness at metaphase. These are immun-ostained with anti-topoisomerase II antibodies. From Boy de la Tour and Laemmli.280 Courtesy of U. K. Laemmli.

Pack, P., Kujau, M, Schroeckh, V., Knupfer, U., Wenderoth, R., Riesenberg, D., and Pluckthun, A. (1993) Improved bivalent miniantibodies, with identical avidity as whole antibodies, produced by high cell-density fermentation of Escherichia coll. Biotechnology 11, 1271-1277... 

Another important consequence of the branched structure may well be the ability of the type 1 and type 2 determinants on a single branch to combine with two sites on the same antibody molecule. Such a bivalent interaction would provide very strong binding as Karush (63) has shown for other systems. 

Fig. 2.3 Schematic of antibody immunoglobulin G (IgG). It is a bivalent bioligand with binding sites formed by light-chain fragments Fab...

Bivalent and Bispecific Monoclonal Antibodies in Cancer Therapy... 

Bivalent and bispecific monoclonal antibodies have many practical applications, including immunodiagnosis and immunotherapy. Bivalency can allow antibodies to bind... 

Kaufman, E.N. and Jain, R.K. (1992) Effect of bivalent interaction upon apparent antibody affinity experimental confirmation of theory using fluorescence photobleaching and implications for antibody binding assays. Cancer Res., 52,4157 1167. 

---