title: Identification of novel mimicry epitopes for cardiac myosin heavy chain-α that induce autoimmune myocarditis in A/J mice.
abstract: Myocarditis is one cause of sudden cardiac death in young adolescents, and individuals affected with myocarditis can develop dilated cardiomyopathy, a frequent reason for heart transplantation. Exposure to environmental microbes has been suspected in the initiation of heart autoimmunity, but the direct causal link is lacking. We report here identification of novel mimicry epitopes that bear sequences similar to those in cardiac myosin heavy chain (MYHC)-α 334-352. These epitopes represent Bacillus spp., Magnetospirillum gryphiswaldense, Cryptococcus neoformans and Zea mays. The mimicry peptides induced varying degrees of myocarditis in A/J mice reminiscent of the disease induced with MYHC-α 334-352. We demonstrate that the mimics induce cross-reactive T cell responses for MYHC-α 334-352 as verified by MHC class II IA(k)/tetramer staining and Th-1 and Th-17 cytokines similar to those of MYHC-α 334-352. The data suggest that exposure to environmental microbes which are otherwise innocuous can predispose to heart autoimmunity by molecular mimicry.
authors.affiliation: School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, United States.
authors.forename: Chandirasegaran
authors.initials: C
authors.lastname: Massilamany
authors.forename: Arunakumar
authors.initials: A
authors.lastname: Gangaplara
authors.forename: David
authors.initials: D
authors.lastname: Steffen
authors.forename: Jay
authors.initials: J
authors.lastname: Reddy
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics; D000946:Antigens, Fungal / Q000737:chemistry / Q000235:genetics; D052179:Antigens, Plant / Q000737:chemistry / Q000235:genetics; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology*; D001407:Bacillus / Q000235:genetics / Q000276:immunology; D024722:Cardiac Myosins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D003429:Cross Reactions; D003455:Cryptococcus neoformans / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D000939:Epitopes / Q000737:chemistry / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D042201:Magnetospirillum / Q000235:genetics / Q000276:immunology; D051379:Mice; D008805:Mice, Inbred A; D018716:Molecular Mimicry / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D009205:Myocarditis / Q000209:etiology / Q000276:immunology*; D018995:Myosin Heavy Chains / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D003313:Zea mays / Q000235:genetics / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D000946:Antigens, Fungal; D052179:Antigens, Plant; D016207:Cytokines; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D024722:Cardiac Myosins; D018995:Myosin Heavy Chains