Anti-idiotypic antibody D12 and superantigen SPA both interact with human V(H)3-encoded antibodies on the external face of the heavy chain involving FR1, CDR2 and FR3

The mouse monoclonal antibody (mAb) D12 specifically binds in the variable region (idiotype) of human V(H)3 encoded antibodies. We used mutational ana lysis to determine the subregions of a V(H)3 encoded antibody which effect the interaction with mAb D12. Recombinant antibodies composed of mutant hea vy chains were produced using the baculovirus expression system. The result s of this topographical study indicate that the combined conformations of F R1, CDR2 and FR3 are critical for mAb D12 binding. MAb D12 binding was not effected either by the heavy chain CDR3 sequence nor by the light chain. We previously demonstrated that structures within the same three subregions a re required for the B cell superantigen Staphylococcal protein A (SPA) bind ing to V(H)3 encoded antibodies. Thus, some anti-idiotypic antibodies can i nteract with antibodies in a similar fashion to superantigens. (C) 1999 Els evier Science Ltd. All rights reserved.