Idiotypic antibodies, production

Idiotypic network. Idiotypic determinants (idiotypes) are unique antigenic epitopes characteristic of the antigen receptors on the surface of T and B cells. They are associated with the variable regions of these receptors. Antibodies produced by B cells as the result of antigenic stimulation can themselves stimulate the production of auto-anti-idiotypic antibodies which have the ability to combine with the B-cell receptor (Ig) and thus can dampen down the immune response. Idiotypes may likewise stimulate the production of T cells specific for idiotypic determinants. Jerne (1974) postulated his... 

Figure 26 Production of abzymes using the anti-idiotypic antibodies method.

Development of such idiotype-dependent assays requires much labor and a long period because two-step antibody production is necessary first, immunization with a hapten-carrier conjugate to produce a specific anti-hapten antibody, then a second immunization with the anti-hapten antibody for generating two types of anti-idiotype antibodies. Furthermore, a suitable combination between a-type and /3-type antibodies, whose binding to the anti-hapten antibody is competitive, has to be found. 

Schick, M. R., and Kennedy, R. C., Production and characterization of anti-idiotypic antibody reagents. Methods Enzymol. 178,36-48 (1989). 

Eichmann, K. (1974). Idiotype suppression. I. Influence of the dose and of the effector functions of anti-idiotypic antibody on the production of an idiotype. Eur. J. Immunol. 4,296-302. 

Siekevitz, M., Huang, S.Y., Gefter, M.L. (1983). The genetic basis of antibody production a single heavy chain variable region gene encodes all molecules bearing the dominant anti-arsonate idiotype in the strain A mouse. Eur. J. Immunol. 13, 123-132. 

Another approach to the preparation of antibodies against the prolactin receptor has involved the production of anti-idiotypic antibodies against anti-prolactin antibodies [53], Such antibodies were able to compete with prolactin for binding to the receptor. 

Thielemans, K. Maloney, D.G. Meeker, T. Eujimoto, J. Doss, C. Warnke, R.A. Bindl, J. Gralow, J. Miller, R.A. Levy, R. Strategies for production of monoclonal anti-idiotype antibodies against human B-cell lymphomas. J.Immunol. 1984,133, 495-501. 

Conjugated monoclonal antibodies can be used as carriers of toxic therapy, such as radionuclides, (e.g., yttrium-90 ibritumomab tiuxetan and iodine-131 tositumomab), cytotoxic drugs, or cell toxins to specific cell targets. They are also being employed to create tumor vaccines by stimulating a host antibody reaction causing the production of anti-idiotype antibodies. 

All theoretical elegance notwithstanding, it is laborious and risky to take the route of anti-idiotypic antibodies. You have to process the ligands for the immunization, set up one or several detection assays, and carry out at least two immunizations whose success depends on luck (Table 6.1). A beginner needs years to produce useful anti-idiotypic antibodies. Typically, antibodies have only minimal practical value by the time they become available. During the years of their production, the tactical situation in the area has often changed drastically. 

Kits for oral hyposensitization to Compositae ivy are no longer available. Because biological agents are difficult to standardize, trying this without a commercial product is not recommended. Some oral hyposensitization methods have been somewhat effective, perhaps because of the development of anti-idiotypic antibodies [103]. 

Gearhart, P.J., Sigal, N.H., Klinman, N.R. (1975). Production of antibodies of identical idiotype but diverse immunoglobulin classes by cells derived from a single stimulated B cell. Proc. Natl. Acad. Sci. USA 72, 1707-1711. 

Czop JK, Gurish MF, Kadish JL (1990) Production and isolation of rabbit anti-idiotyp-ic antibodies directed against the human monocyte receptor for yeast P-glucans. J Immunol 145 995-1001... 

The existence of strong idiotypic cross-reactions among different mice of the same strain, with respect to certain antigens, made it feasible to attempt suppression of a particular idiotype with antiidiotypic antiserum. This could be analogous to suppression of an allotype in heterozygous animals with antiallotypic antiserum (Chapter 9). The appearance of an idiotype, characteristic of anti-p-azophenylarsonate (anti-Ar) antibodies of A/J mice was suppressed for periods up to 5 months, in neonatal or adult A/J mice, by intraperitoneal administration of a saline solution of 2 or 4 mg of an IgG fraction of rabbit anti-D antiserum (103). It was shown that suppression is not caused by simple absorption of anti-Ar antibodies by the antiidiotypic antibodies injected. There was no concomitant suppression of the total antihapten response or of production of antibody to the protein carrier. 

Immunological memory, for the production of the cross-reactive idiotype, can also be suppressed after primary immunization with the phenylarsonate-protein conjugate (104a). This observation indicates that memory cells are subject to inactivation by heterologous antiidiotype antibodies and, also, that they are accessible in vivo. 

Immobilized antibodies for the production of an active immobilized derivative of the homologous enzyme antigen Quantitative determination of idiotypic markers by radioimmunoassay... 

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