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Identification of Streptococcal M-Protein Cardiopathogenic Epitopes in Experimental Autoimmune Valvulitis |
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| Authors: | Christine A Kirvan Jeffrey E Galvin Silvia Hilt Stanley Kosanke Madeleine W Cunningham |
| Institution: | 1. Department of Biological Sciences, California State University, Sacramento, CA, USA 2. Zoetis, Lincoln, NE, USA 3. Department of Pathology, University of Oklahoma, HSC, Oklahoma City, OK, USA 4. Department of Microbiology and Immunology, University of Oklahoma, HSC, Biomedical Research Center, Room 217, 975?N.E. 10th Street, Oklahoma City, OK, 73104, USA |
| Abstract: | The M protein of rheumatogenic group A streptococci induces carditis and valvulitis in Lewis rats and may play a role in pathogenesis of rheumatic heart disease. To identify the epitopes of M5 protein that produce valvulitis, synthetic peptides spanning A, B, and C repeat regions contained within the extracellular domain of the streptococcal M5 protein were investigated. A repeat region peptides NT4, NT5/6, and NT7 induced valvulitis similar to the intact pepsin fragment of M5 protein. T cell lines from rats with valvulitis recognized M5 peptides NT5/6 and NT6. Passive transfer of an NT5/6-specific T cell line into naïve rats produced valvulitis characterized by infiltration of CD4+ cells and upregulation of VCAM-1, while an NT6-specific T cell line did not target the valve. Our new data suggests that M protein-specific T cells may be important mediators of valvulitis in the Lewis rat model of rheumatic carditis. |
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