Antibodies anti-metatype

Assay Systems Based on Anti-metatype Antibodies. 162... 

The invention of B cell hybridoma technology (K3) has allowed the generation of various kinds of useful antibodies, even very minor or rare antibody species elicited in serum by the conventional procedure, as a pure immunochemical reagent in almost unlimited amounts. Among such new-generation monoclonal antibodies, anti-idiotype antibodies and anti-immune complex (anti-metatype) antibodies have been successfully introduced as key reagents enabling noncompetitive hapten immunoassays (Fig. 11). 

Fig. 11. Schematic representation of the binding properties of anti-idiotype antibodies and antimetatype antibodies. V, hapten a-Id, a-type anti-idiotype antibody /i-Id, /i-type anti-idiotype antibody Met, anti-metatype antibody anti-C-region, antibodies recognizing the constant region of a primary antibody (recognizing isotype or allotype).

The assay principle should, however, be applicable to any target hapten, unlike assays based on a chemical modification. Cloning efficiency of the hybridoma-secreting anti-idiotype antibodies would be in a practical range, and much higher than that of anti-metatype antibodies. We (Kl) established four kinds of a-type and two kinds of /3-type anti-idiotype antibodies after three fusion experiments, each using spleen cells from one immunized mouse. Barnard et al. (Bl, B3, B4)... 

Using an antibody specifically recognizing the antigen-antibody complex, more direct noncompetitive hapten immunoassays, which can be regarded as semi two-site immunometric assay, could be established (S3). Figure 14 depicts two typical procedures of noncompetitive assays using anti-metatype antibodies, which are based on principle C in Fig. 4. 

Fig. 14. Noncompetitive hapten immunoassay procedures (A, Bl, and B2) using an anti-metatype antibody recognizing the immune complex between a hapten and the anti-hapten antibody. Anti-hap, anti-hapten antibody (primary antibody) Met, anti-metatype antibody S, signal-generating group.

Kl. Kobayashi, N., Oiwa, H., Kubota, K., Sakoda, S., and Goto, J., Monoclonal antibodies generated against an affinity-labeled immune complex of an anti-bile acid metabolite antibody An approach to noncompetitive hapten immunoassays based on anti-idiotype or anti-metatype antibodies. J. Immunol. Methods 245, 95-108 (2000). 

V5. Voss, Jr., E. W., and Mummert, M. E., Anti-metatype antibodies in immunoassays. Mikrochim. 

V4. Voss, Jr., E. W., Miklasz, S. D., Petrossian, A., and Dombrink-Kurzman, M. A., Polyclonal antibodies specific for liganded active site (metatype) of a high affinity anti-hapten monoclonal antibody. Mol. Immunol 25, 751-759 (1988). 

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