IDIOTYPIC STUDY OF A BISPECIFIC THYROGLOBULIN AND THYROPEROXIDASE MONOCLONAL-ANTIBODY

We have previously established that thyroperoxidase (TPO), a major thy roid antigen involved in autoimmune thyroid diseases, interacts with a n idiotype present on human and mouse antibodies directed to thryoglob ulin (TG), another thyroid autoantigen. In order to characterize the T PO-reactive idiotype, we selected a TG monoclonal antibody (mAb J7 B49 .15) which bound to TPO and cross-reacted with human bispecific TG and TPO autoantibodies (TGPO aAb) for both TG and TPO binding. The TPO-re active structure of the mAb J7 B49.15 was present on the F(ab')(2), lo cated next to the TG binding site and dependent on the association of the heavy and light chains. We found that mAb J7 B49.15 shared a TPO-r eactive idiotypic structure with TG mAb from the same cluster of TG re activity. All the mAb from this cluster were directed to an immunodomi nant region of TG, recognized by TG aAb. Natural anti-idiotypes from p ooled normal human IgG used as a therapeutic intravenous preparation i nhibited the TPO binding to mAb J7 B49.15. By homologous immunization in BALB/c mice, mAb J7 B49.15 induced an antiserum with both TG and TP O reactivities. Whereas TG reactivity decreased as early as day 14 pos t-immunization, TPO reactivity remained at a plateau value from day 21 to day 42. The TG and TPO reactive antisera were shown to inhibit the binding of mAb J7 B49.15 to TG and TPO, respectively. We concluded th at mAb J7 B49.15 reacted with TPO through an interspecies idiotype whi ch appeared conformational and related to the epitopic specificity of the mAb. Interestingly, this idiotype would carry the internal image o f a TG structure able to induce, in homologous system, a TG antibody r esponse followed by a TPO response without the need of any immunizing antigen. (C) 1996 Academic Press Limited