PREVENTION OF EXPERIMENTAL AUTOIMMUNE MYASTHENIA-GRAVIS BY A MONOCLONAL-ANTIBODY TO A COMPLEMENTARY PEPTIDE FOR THE MAIN IMMUNOGENIC REGIONOF THE ACETYLCHOLINE-RECEPTOR

We have previously reported that a complementary peptide (denoted RhCA 67-16), encoded by RNA complementary to that of the Torpedo acetylcho line receptor (AChR) main immunogenic region (MIR), AChR residues alph a 61-76, induces polyclonal and monoclonal Ab reactive with Ig against the AChR MIR. RhCA 67-16 vaccination also protected against the devel opment of experimental autoimmune myasthenia gravis (EAMG) in Lewis ra ts. In the present report, we found that a mAb (denoted TCM 240, IgG1 kappa) against RhCA 67-16 recognized three different idiotypic Ab (mAb 6, mAb 35, and mAb 198), which were previously reported by others to recognize the AChR MIR and to cause EAMG. Based on these results, TCM 240 was tested for prophylactic effects in EAMG. EAMG induced passivel y by mAb 35 was inhibited by simultaneous injection with TCM 240. The disease severity was inversely paralleled by the ratio of mAb 35 to TC M 240. EAMG induced by immunization with purified native Torpedo AChR was also inhibited by TCM 240, but not a control mAb. The inhibitory e ffect of TCM 240 on actively induced EAMG occurred without significant ly lowering the overall AChR Ab levels, which indicates a limited repe rtoire of disease-causing Ab in EAMG and perhaps MG. Such findings sug gest the existence of an EAMG-associated Id and also support the conce pt of an MIR. In a more general sense, these results demonstrate that prophylactic and perhaps diagnostic mAb for autoimmune diseases can be produced by immunization with complementary peptides for disease-asso ciated epitopes.