Enzyme mimicry by the antiidiotypic antibody approach

The concept of "internal image" of antiidiotypic antibodies has provided th e basis for eliciting catalytic antibodies. A monoclonal IgM 9A8 that was o btained as an antiidiotype to AE-2 mAb, a known inhibitor of acetytcholines terase, displayed esterolytic activity. Study of recombinant Fab fragments and separate light and heavy chains of 9A8 confirmed that the antibody vari able domain encodes the catalytic function, whereas neither part of the pri mary sequence of the Fab exhibited homology with the enzyme. The specific m odification of the 9A8 variable domain by an active site-directed covalent inhibitor revealed the presence of an active site Ser residue. A three-dime nsional modeling suggests the existence of a functional catalytic dyad Ser- His. Comparison of active sites of 9A8 and 17E8 esterolytic abzyme raised a gainst transition-state analog revealed structural similarity although both antibodies were elicited by two different approaches.