Mimicry of human IgE epitopes by anti-idiotypic antibodies

According to Jerne's network hypothesis, the binding site of an anti-idioty pic antibody also represents the internal image of an epitope present on a foreign, or even a self antigen. In recent years, antigen mimicry has been defined at the molecular level for some xeno-antigens. However, until now t here has been no demonstration of structural mimicry between a human anti-i diotypic antibody and a self structure. To address this question, we used h uman IgE as the self structure and a well-defined anti-human IgE mAb (BSW17 ). We describe the isolation of two antiidiotypic antibodies specific for t he anti-IgE antibody BSW17 from a non-immune human Fab phage display librar y. Interestingly, these two anti-idiotypic antibodies mimic the same molecu lar surface region as a previously described IgE peptide mimotope isolated by panning on BSW17, but they cover a much larger epitope on the IgE molecu le. Accordingly, immunisation of rabbits with the two anti-idiotypic antibo dies induced high-affinity antibodies with the same characteristics as BSW1 7. Thus, our data demonstrate that it is possible to isolate anti-idiotypic antibodies derived from the human genome without the need for hyperimmunis ation, and confirm Jerne's hypothesis that both foreign antigens and self s tructures can be mimicked by our own immunoglobulins. (C) 2000 Academic Pre ss.