May 1, 1996

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

The Journal of Clinical Investigation
C PummererN Neu

Abstract

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 ...Continue Reading

Mentioned in this Paper

Immune System
T-Lymphocyte
Ventricular beta-Myosin
Variolation
Mice, Inbred BALB C
Pathogenic Organism
Myocardium
Soleus Muscle Structure
Little's Disease
Peptide Fragments

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