IDENTIFICATION OF MYOCARDITOGENIC PEPTIDES DERIVED FROM CARDIAC MYOSIN CAPABLE OF INDUCING EXPERIMENTAL ALLERGIC MYOCARDITIS IN THE LEWIS RAT - THE UTILITY OF A CLASS-II BINDING MOTIF IN SELECTING SELF-REACTIVE PEPTIDES

Cardiac myosin (CM) has been implicated as an autoantigen in the induc tion of experimental allergic myocarditis (EAM). At the present time n o myocarditogenic peptides of CM have been identified. To identify CM peptides with myocarditogenic properties we have made use of a putativ e binding motif for the MHC class II molecule RT1.B-1 in the rat. The amino acid sequence of CM alpha-chain was scanned and found to contain nine peptides that contain this binding motif, three peptides found o nly in the cardiac form of myosin were chosen for further study. This manuscript describes the identification of two CM peptides capable of inducing EAM in the Lewis rat. In doing so this study demonstrates the utility of an MHC class II binding motif to (correctly) predict patho genic, autoimmunity inducing, peptides. Peptides, CM 1, and CM 2 are t he first peptides described that are capable of inducing EAM in rats. The utilization of CM 2 peptide has permitted the establishment of a l ong term, Ag specific cell line capable of adoptively transferring EAM . Moreover, the establishment of CM 2 specific T lymphocyte lines has permitted the description of a detailed proliferative response of a my ocarditogenic cell line to a specific cardiac Ag. The identification o f CM 1 and 2 formally proves that CM, and not a co-purified contaminan t, is an Ag in EAM. Finally, this report documents that experimentally induced giant cell myocarditis is not a separate disease entity arisi ng from a distinct cardiac Ag or CM epitope from regular myocarditis.