PREVENTION OF EXPERIMENTAL AUTOIMMUNE MYASTHENIA-GRAVIS BY MANIPULATION OF THE IMMUNE NETWORK WITH A COMPLEMENTARY PEPTIDE FOR THE ACETYLCHOLINE-RECEPTOR

Myasthenia gravis (MG) and experimental autoimmune myasthenia gravis ( EAMG) are caused, in part, by the production of autoantibodies against the main immunogenic region, amino adds 61-76, of the alpha chain of the acetycholine receptor (AChR). Theoretically, induction of anti-idi otypic (Id) antibodies (Abs) should be a highly specific treatment for the disease by virtue of their potential ability to neutralize Abs to the AChR. We have tested this idea by attempting to evoke such anti-I d Abs by immunization with a peptide (termed RhCA 67-16) encoded by RN A complementary to the Torpedo AChR main immunogenic region and determ ining whether such treatment will prevent the development of EAMG. Imm unization with RhCA 67-16, but not a control peptide termed PBM 9-1, w as found to elicit the production of anti-Id Abs that blocked recognit ion of native Torpedo AChR by its Ab. This anti-Id Ab activity was abl ated by incubation of the anti-RhCA 67-16 serum with RhCA 67-16, but n ot PBM 9-1, prior to the assay for Ab binding to AChR. The anti-Id Ab- inducing activity of RhCA 67-16 was confirmed by the ability to produc e a rat monoclonal Ab to RhCA 67-16 that showed anti-Id activity for p olyclonal rat Ab reactive with AChR residues 67-76. Most importantly, RhCA 67-16 immunization also prevented the development of EAMG in Lewi s rats challenged with Torpedo AChR (25% incidence versus 90% in the c ontrols) and diminished the AChR Ab levels in animals injected with lo w doses of AChR. Our results suggest a therapy for MG and perhaps othe r autoimmune diseases through the induction of anti-Id Abs by peptide immunogens.