title: Identification of streptococcal m-protein cardiopathogenic epitopes in experimental autoimmune valvulitis.
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.
authors.affiliation: Department of Biological Sciences, California State University, Sacramento, CA, USA.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Kirvan
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Galvin
authors.forename: Silvia
authors.initials: S
authors.lastname: Hilt
authors.forename: Stanley
authors.initials: S
authors.lastname: Kosanke
authors.forename: Madeleine W
authors.initials: MW
authors.lastname: Cunningham
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology* / Q000382:microbiology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology / Q000637:transplantation; D002352:Carrier Proteins / Q000276:immunology*; D002460:Cell Line; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte; D005260:Female; D006349:Heart Valve Diseases / Q000276:immunology* / Q000382:microbiology; D010446:Peptide Fragments / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D012214:Rheumatic Heart Disease / Q000276:immunology* / Q000382:microbiology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; D019010:Vascular Cell Adhesion Molecule-1; C014689:streptococcal M protein