Identification of cardiac myosin peptides capable of inducing autoimmune myocarditis in BALB/c mice.

CL Pummerer, K Luze, G Grässl… - The Journal of …, 1996 - Am Soc Clin Investig
CL Pummerer, K Luze, G Grässl, K Bachmaier, F Offner, SK Burrell, DM Lenz, TJ Zamborelli…
The Journal of clinical investigation, 1996Am Soc Clin Investig
Immunization with cardiac myosin induces T cell-mediated myocarditis in genetically
predisposed mice and serves as a model for autoimmune heart disease. This study was
undertaken to identify pathogenic epitopes on the myosin molecule. Our approach was
based on the comparison of the pathogenicity between cardiac (alpha-) myosin and soleus
muscle (beta-) myosin. We show that alpha-myosin is the immunodominant isoform and
induces myocarditis at high severity and prevalence whereas beta-myosin induces little …
Immunization with cardiac myosin induces T cell-mediated myocarditis in genetically predisposed mice and serves as a model for autoimmune heart disease. This study was undertaken to identify pathogenic epitopes on the myosin molecule. Our approach was based on the comparison of the pathogenicity between cardiac (alpha-)myosin and soleus muscle (beta-)myosin. We show that alpha-myosin is the immunodominant isoform and 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 sequence between alpha- and beta-myosin isoforms. Cardiac myosin peptides corresponding to these regions of difference were synthesized and tested for their ability to induce inflammatory heart disease. Three pathogenic peptides were identified. One peptide that is located in the head portion 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.
The Journal of Clinical Investigation