T cell mimicry in inflammatory heart disease.
Inflammatory heart diseases such as myocarditis and rheumatic heart disease result from the infiltration of the myocardium or valve with T cells and macrophages that result in scarring of the myocardium or valve and alteration in cardiac function. Our studies of T cells from these diseases have identified cardiac myosin in both rheumatic carditis and myocarditis as an important autoantigen. In rheumatic heart disease, streptococcal M protein specific T cells migrate to valves. By investigating streptococcal M protein and cardiac myosin in the Lewis rat model of myocarditis and valvulitis, T cell mimicry is supported as a potential mechanism in disease. Structural and immunological mimicry between the streptococcal M protein and cardiac myosin is shown directly in the Lewis rat model. Rat T cell lines demonstrate mimicry between cardiac myosin and M protein, and T cells isolated directly from inflammatory lesions in myocarditis respond to streptococcal M protein peptides. Studies in BALB/c mice also support the immunological crossreactivity of T cells primed against cardiac myosin with streptococcal M protein peptides containing cardiac myosin homologies. T cell lines produced from the Lewis rat specific to the cardiac myosin like sequences of streptococcal M protein migrated to the valves after passive transfer of the M protein specific T cell lines. In coxsackieviral myocarditis in the MRL mouse strain, cardiac myosin mimicking M protein peptide NT4 was found to induce tolerance and prevent coxsackieviral induced myocarditis, suggesting T cell mimicry between coxsackievirus and streptococcal M protein, both of which are associated with inflammatory heart disease. T cell mimicry between cardiac myosin and microbial antigens such as the streptococcal M protein may prime the immune system for inflammatory heart disease.
Cunningham
Madeleine W
MW
Department of Microbiology and Immunology, Biomedical Research Center, University of Oklahoma Health Sciences Center, Room 217, 975 NE 10th Street, Oklahoma City, OK 73104, USA. madeleine-cunningham@ouhsc.edu
D000818:Animals; D000942:Antigens, Bacterial; D015551:Autoimmunity / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D024722:Cardiac Myosins / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology; D004770:Enterovirus / Q000276:immunology; D006801:Humans; D051379:Mice; D018716:Molecular Mimicry / Q000276:immunology*; D009205:Myocarditis / Q000276:immunology*; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology*
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; C014689:streptococcal M protein; D024722:Cardiac Myosins