title: Identification of an Epitope from Adenine Nucleotide Translocator 1 That Induces Inflammation in Heart in A/J Mice.
abstract: Heart failure, a leading cause of death in humans, can emanate from myocarditis. Although most individuals with myocarditis recover spontaneously, some develop chronic dilated cardiomyopathy. Myocarditis may result from both infectious and noninfectious causes, including autoimmune responses to cardiac antigens. In support of this notion, intracellular cardiac antigens, like cardiac myosin heavy chain-α, cardiac troponin-I, and adenine nucleotide translocator 1 (ANT1), have been identified as autoantigens in cardiac autoimmunity. Herein, we demonstrate that ANT1can induce autoimmune myocarditis in A/J mice by generating autoreactive T cells. We show that ANT1encompasses multiple immunodominant epitopes (namely, ANT121-40, ANT131-50, ANT1171-190, and ANT1181-200). Although all four peptides induce comparable T-cell responses, only ANT121-40 was found to be a major myocarditogenic epitope in immunized animals. The myocarditis-inducing ability of ANT121-40 was associated with the generation of T cells producing predominantly IL-17A, and the antigen-sensitized T cells could transfer the disease to naïve recipients. These data indicate that cardiac mitochondrial proteins can be target autoantigens in myocarditis, supporting the notion that the antigens released as a result of primary damage may contribute to the persistence of chronic inflammation through autoimmunity.
authors.affiliation: School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska.
authors.forename: Rakesh H
authors.initials: RH
authors.lastname: Basavalingappa
authors.affiliation: School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska.
authors.forename: Chandirasegaran
authors.initials: C
authors.lastname: Massilamany
authors.affiliation: School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska.
authors.forename: Bharathi
authors.initials: B
authors.lastname: Krishnan
authors.affiliation: School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska.
authors.forename: Arunakumar
authors.initials: A
authors.lastname: Gangaplara
authors.affiliation: Nebraska Center for Virology and School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska.
authors.forename: Guobin
authors.initials: G
authors.lastname: Kang
authors.affiliation: Department of Biological Systems Engineering, University of Nebraska-Lincoln, Lincoln, Nebraska.
authors.forename: Vahid
authors.initials: V
authors.lastname: Khalilzad-Sharghi
authors.affiliation: Department of Biological Systems Engineering, University of Nebraska-Lincoln, Lincoln, Nebraska.
authors.forename: Zhongji
authors.initials: Z
authors.lastname: Han
authors.affiliation: Department of Biological Systems Engineering, University of Nebraska-Lincoln, Lincoln, Nebraska.
authors.forename: Shadi
authors.initials: S
authors.lastname: Othman
authors.affiliation: Nebraska Center for Virology and School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska.
authors.forename: Qingsheng
authors.initials: Q
authors.lastname: Li
authors.affiliation: Center for Biotechnology, University of Nebraska-Lincoln, Lincoln, Nebraska.
authors.forename: Jean-Jack
authors.initials: JJ
authors.lastname: Riethoven
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, California.
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Sobel
authors.affiliation: School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska.
authors.forename: David
authors.initials: D
authors.lastname: Steffen
authors.affiliation: School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska. Electronic address: nreddy2@unl.edu.
authors.forename: Jay
authors.initials: J
authors.lastname: Reddy
mesh_terms: D033741:Adenine Nucleotide Translocator 1 / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D024722:Cardiac Myosins / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000209:etiology / Q000503:physiopathology*; D000939:Epitopes; D005260:Female; D006321:Heart / Q000503:physiopathology; D006801:Humans; D007249:Inflammation; D020381:Interleukin-17 / Q000378:metabolism; D051379:Mice; D024101:Mitochondrial Proteins / Q000276:immunology / Q000378:metabolism; D009205:Myocarditis / Q000150:complications / Q000276:immunology* / Q000503:physiopathology; D013601:T-Lymphocytes / Q000276:immunology; D019210:Troponin I / Q000276:immunology
chemical_list: D033741:Adenine Nucleotide Translocator 1; D001324:Autoantigens; D000939:Epitopes; D020381:Interleukin-17; D024101:Mitochondrial Proteins; D019210:Troponin I; D024722:Cardiac Myosins