IDENTIFICATION OF CARDIAC MYOSIN PEPTIDES CAPABLE OF INDUCING AUTOIMMUNE MYOCARDITIS IN BALB C MICE/

Immunization with cardiac myosin induces T cell-mediated myocarditis i n genetically predisposed mice and serves as a model for autoimmune he art disease, This study was under-taken to identify pathogenic epitope s on the myosin molecule, Our approach was based on the comparison of the pathogenicity between cardiac (alpha-) myosin and soleus muscle (b eta-) myosin. We show that alpha-myosin is the immunodominant isoform acid induces myocarditis at high severity and prevalence whereas; beta -myosin induces little disease. Therefore the immunodominant epitopes of alpha-myosin must reside in regions of different amino acid sequenc e between alpha- and beta-myosin isoforms, Cardiac myosin peptides cor responding to these regions of difference were synthesized and tested for their ability to induce inflammatory heart disease, Three pathogen ic peptides were identified. One peptide that is located in the head p ortion of the molecule induced severe myocarditis, whereas two others that reside in the rod portion possessed only minor pathogenicity, The identification of pathogenic epitopes on the cardiac myosin molecule will allow detailed studies on the recognition of this antigen by the immune system and might be used to downmodulate ongoing heart disease.