Antigens univalent

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. 

Turning on B cells. B lymphocytes, the precursors of plasma cells, are triggered to proliferate by the binding of multivalent antigens to receptors on their surfaces. The cell-surface receptors are transmembrane immunoglobulins. Univalent antigens, in contrast, do not activate B cells. 

Many epitopes of different kinds, but only one of each kind on one antigen molecule multideterminate and univalent. Most protein antigens fall into this category. 

Agglutination occurs only over a certain range of serum dilutions because of either antigen or antibody excess. In the prozone, a large excess of antibody is present, so that each antibody behaves univalently and cross-linking does not occur (Eq. 5.5) ... 

At very high serum dilutions, a large excess of antigen exists, so that not enough antibody is present to cross-link the antigen and cause agglutination. In this case, the antigen behaves in a univalent manner (Eq. 5.6) ... 

Secondary reactions such as agglutination and precipitation are generally used to identify or screen for the presence of certain suspected antibodies or antigens. They require antigens to be either multivalent, or multideterminate, or both, to allow crosslinking to occur. Secondary reactions cannot be used to quantitate or identify haptens, since haptens are always unideterminate and univalent. 

Accordingly, when the system is working optimally the amount of hemolysis is quantitatively and inversely proportional to the amount of antigen added to the system. The hemolysis can be read spectro-photometrically (B9, M12), or the red blood cells can be tagged with Cr, and the amount of lysis determined by counting the amount of Cr which becomes soluble after lysis has occurred (B12). Not all antigen-antibody reactions will fix complement e.g., horse antisera do not, nor do univalent antibody-antigen systems (A12). 

The strength of the antigen-antibody complex is called the affinity or avidity. Affinity refers to the intrinsic association constant between an antibody and a univalent antigen, while avidity refers to the overall binding energy between antibodies and a multivalent antigen. We can write the overall binding reaction as... 

Alkan SS, Bush ME, Nitecki DE, Goodman JW (1972 b) Antigen recognition and the immune response. Structural requirements in the side chain of tyrosine for immunogenicity of L-tyrosine-azobenzenearsonate. J Exp Med 136 387-391 Amkraut AA, Rosenberg LT, Raffel S (1963) Elicitation of PCA by univalent and divalent haptens. J Immunol 91 644-650... 

Levine BB (1960 c) Formation of D-penicillamine-cysteine mixed disulphide by reaction of D-benzylpenicilloic acide with cysteine Nature 187 940 Levine BB (1961) Studies on the formation of the penicillin antigen. II. Some reactions of D-benzylpenicillenic acid in aqueous solution at pH 7.5. Arch Biochem Biophys 93 50 Levine BB (1962) N(a-D-penicilloyfamines as univalent hapten inhibitors of antibody-de-pendent allergic reactions to penicillin. J Med Chem 5 1025 Levine BB (1963) Studies on the dimensions of the rabbit anti-benzyl penicilloyl antibody combining sites. J Exp Med 117 161... 

In the ideal case, the binding of a univalent antigen (hapten) to a single antibody-binding site can be represented by the law of mass action, such that at equilibrium... 

The phenomenon of hapten inhibition has been explained by Landsteiner as resulting from combination of hapten and antibody to form a soluble complex, thus effectively neutralizing the antibody. The formation of soluble complex instead of a precipitate by antibody and hapten is explained by the framework theory as the result of the univalence of the hapten. It might be expected that as the maximum amount of precipitate which can be obtained from a serum is decreased by addition of hapten there would occur a corresponding decrease in the optimum antigen concentration, as was observed in the dilution experiments. 

The only theory of the precipitation reaction which, following the program begun by Arrhenius, has been developed by straightforward application of the principles of chemical equilibrium is that of Pauling, Pressman, Campbell and Ikeda (19). This theory applies only to relatively simple systems, namely, those composed of bivalent antigen and bivalent antibody, univalent hapten, certain soluble complexes, and precipitate with invariant composition AB. 

Let us now ask to what extent this experimental result supports the framework theory— whether it might not be equally compatible with some other theory. The answer is that our experiment shows that both of the two haptenic groups R and X of the RX molecule enter into specific combination with antibody, that the molecule of precipitating antigen is hence truly bivalent, and that this bivalence is necessary for precipitation. This, however, is common to two theories— the framework theory, which requires that the antibody molecules, as well as the antigen molecules, be bivalent or multivalent, and an alternative theory, which is based on the assumption that a complex of a multivalent antigen molecule and two or more univalent antibody molecules is... 

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