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The concept of antigen internal image was applied to the production of catalytic antibodies. An antibody raised in rabbits to DNase (Ab1), acted as a competitive inhibitor of the catalysis, and thus was assumed to contain anti-active site Ab. This Ab1 was used to elicit a polyclonal anti-idiotypic antibody (Ab2). This later exhibited a DNA recognition specificity, suggesting the existence of structural internal images mimicking the conformation of the active site. Moreover, Ab2 were able to hydrolyse DNA, indicating the existence of internal images mimicking the enzymatic activity of DNase. Consequently, a strategy can thus be considered using the idiotypic way, for the production of abzymes in the form of internal images of enzyme active sites.

The diversity of a polyclonal anti-idiotypic response (Ab2) to a murine monoclonal anti-A (Ab1) was investigated after purification of two Ab2 populations. One was eluted from human polyclonal anti-A column and the other from Ab1. Analysis of the Ab specificity, as well as screening of the clonotypic distribution, were achieved after splitting Ab by IEF; this was followed by immunoblotting and probing with various anti-ABH mAb. The first population reacted with almost all the murine anti-ABH mAb, as well as with four human anti-A mAb, and consequently consisted of Ab2 beta. The second was composed of "true" Ab2 directed against Ab1. In the first population internal images mimicked either A Ag, or H Ag, or some epitopes common to both. This study demonstrates the plurality of internal images-bearing Ig molecules, some mimicking completely, and some only partially or even unfaithfully the nominal A determinant. The analysis of this idiotypic cascade proves the existence of a degeneracy of the initial restricted antigenic specificity. The consequences of such a process are discussed.