INHIBITION OF EXPERIMENTAL AUTOIMMUNE MYASTHENIA-GRAVIS BY MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II COMPETITOR PEPTIDES RESULTS NOT ONLY IN A SUPPRESSED BUT ALSO IN AN ALTERED IMMUNE-RESPONSE

To assess the capacity of major histocompatibility complex (MHC) class II- binding competitor peptides in inhibiting antibody-mediated disea se processes, we studied experimental autoimmune myasthenia gravis in Lewis rats. Experimental autoimmune myasthenia gravis, a disease model mediated by T cell-dependent autoantibodies against acetylcholine rec eptors, was induced by immunization with Torpedo californica acetylcho line receptor emulsified in complete Freund's adjuvant. The immunodomi nant acetylcholine receptor T cell epitope was recognized by T cells i n the context of MHC class II RT1.B-L. The disease inhibitory capacity of RT1.B-L-binding peptides not related to the acetylcholine receptor was determined upon co-immunization with Torpedo acetylcholine recept or. Co-immunization of peptide OVA323-339, a strong RT1.B-L-binding co mpetitor peptide, resulted in complete disease inhibition. Although, t he priming of the anti-acetylcholine receptor T cell response was not fully inhibited, the kinetics of the response was changed. Moreover, b esides a drastic reduction of the anti-Torpedo acetylcholine receptor antibody titers, a shift in isotype distribution was found. These find ings indicate that antibody-mediated autoimmune processes can be suppr essed by MHC class II competitor peptides. Furthermore, the administra tion of such peptides in vivo not only passively inhibits T cell activ ation, but also functionary alters the immune response.