The applicant has determined that alleles of alpha cardiac myosin heavy chain differ with respect to their ability to induce autoimmune myocarditis. She has also demonstrated that certain strains of mice sequester myosin in their cardiac extracellular matrix and that this sequestration correlates with susceptibility to cardiac injury mediated by anti-myosin antibodies. Based on these data, the applicant plans to identify pathogenic epitopes of murine myosin and to use this information to test the hypothesis that myosin polymorphisms play a role in the development of myocarditis. It is planned to determine which murine anti-myosin antibodies mediate disease and to define the interactions between myosin and extracellular matrix proteins or myocyte membranes that lead to the sequestration of myosin in the extracellular matrix of some mouse strains. The applicant believes these studies will increase our understanding of the importance of polymorphisms of autoantigens and of end organ sensitivity to immune attack in the genetic susceptibility to autoimmune disease. These studies will provide insight into the potential pathogenicity of the anti-myosin response in myocarditis and in other diseases or injuries of the myocardium.
| Malkiel, S; Liao, L; Cunningham, M W et al. (2000) T-Cell-dependent antibody response to the dominant epitope of streptococcal polysaccharide, N-acetyl-glucosamine, is cross-reactive with cardiac myosin. Infect Immun 68:5803-8 |
| Kuan, A P; Chamberlain, W; Malkiel, S et al. (1999) Genetic control of autoimmune myocarditis mediated by myosin-specific antibodies. Immunogenetics 49:79-85 |
