Biochemistry, Biophysics, and Structural Biology Commons^™

The Knowns And Unknowns Of Cardiac Autoimmunity In Viral Myocarditis, Kiruthiga Mone, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Myocarditis can result from various infectious and non‐infectious causes that can lead to dilated cardiomyopathy (DCM) and heart failure. Among the infectious causes, viruses are commonly suspected. But the challenge is our inability to demonstrate infectious viral particles during clinical presentations, partly because by that point, the viruses would have damaged the tissues and be cleared by the immune system. Therefore, viral signatures such as viral nucleic acids and virus-reactive antibodies may be the only readouts pointing to viruses as potential primary triggers of DCM. Thus, it becomes hard to explain persistent inflammatory infiltrates that might occur in individuals affected …

An Evidence For Surface Expression Of An Immunogenic Epitope Of Sarcoplasmic/Endoplasmic Reticulum Calcium-Atpase2a On Antigen-Presenting Cells From Naive Mice In The Mediation Of Autoimmune Myocarditis, Rajkumar Arumugam, Bharathi Yalaka, Chandirasegara Massilamany, Ms Shihabudeen Haider Ali, Ninaad Lasrado, Sabarirajan Jayaraja, Jean-Jack Riethoven, Xinghui Sun, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

We recently reported identification of sarcoplasmic/endoplasmic reticulum calcium-ATPase2a (SERCA2a) 971–990, which induces atrial myocarditis by generating autoreactive T cells in A/J mice. However, it was unknown how antigen-sensitized T cells could recognize SERCA2a 971–990, since SERCA2a-expression is confined to an intracellular compartment. In this report, we present evidence that antigen-presenting cells (APCs) from lymphoid and non-lymphoid organs in naïve animals present SERCA2a 971–990 and stimulate antigen-specific T cells. Using major histocompatibility complex (MHC) class II dextramers for SERCA2a 971–990, we created a panel of T cell hybridomas and demonstrated that splenocytes from naïve A/J mice stimulated the hybridoma cells without …

Viral Myocarditis Involves The Generation Of Autoreactive T Cells With Multiple Antigen Specificities That Localize In Lymphoid And Non-Lymphoid Organs In The Mouse Model Of Cvb3 Infection, Rakesh H. Basavalingappa, Rajkumar Arumugam, Ninaad Lasrado, Bharathi Yalaka, Chandirasegara Massilamany, Arunakumar Gangaplara, Jean-Jack Riethoven, Shi-Hua Xiang, David Steffen, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Autoreactive T cells may contribute to post-viral myocarditis induced with Coxsackievirus B3 (CVB3), but the underlying mechanisms of their generation are unclear. Here, we have comprehensively analyzed the generation of antigen-specific, autoreactive T cells in the mouse model of CVB3 infection for antigens implicated in patients with myocarditis/dilated cardiomyopathy. First, comparative analysis of CVB3 proteome with five autoantigens led us to identify three mimicry epitopes, one each from adenine nucleotide translocator 1 (ANT), sarcoplasmic/ endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) and cardiac troponin I. None of these induced cross-reactive T cell responses. Next, we generated major histocompatibility complex (MHC) class …

Branched Chain Α-Ketoacid Dehydrogenase Kinase 111–130, A T Cell Epitope That Induces Both Autoimmune Myocarditis And Hepatitis In A/J Mice, Bharathi Krishnan, Chandirasegara Massilamany, Rakesh H. Basavalingappa, Arunakumar Gangaplara, Guobin Kang, Qingsheng Li, Francisco A. Uzal, Jennifer L. Strande, Gustavo A. Delhon, Jean-Jack Riethoven, David J. Steffen, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Introduction: Organ-specific autoimmune diseases are believed to result from immune responses generated against self-antigens specific to each organ. However, when such responses target antigens expressed promiscuously in multiple tissues, then the immune-mediated damage may be wide spread.

Methods: In this report, we describe a mitochondrial protein, branched chain α-ketoacid dehydrogenase kinase (BCKD_k) that can act as a target autoantigen in the development of autoimmune inflammatory reactions in both heart and liver.

Results: We demonstrate that BCKD_k protein contains at least nine immunodominant epitopes, three of which, BCKD_k 71–90, BCKD_k 111–130 and BCKD_k 141–160, …

Association Of Autophagy In The Cell Death Mediated By Dihydrotestosterone In Autoreactive T Cells Independent Of Antigenic Stimulation, Ting Jia, Annandurai Anandhan, Chandirasegaran Massilamany, Rajkumar A. Rajasekaran, Rodrigo Franco, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Gender disparity is well documented in the mouse model of experimental autoimmune encephalomyelitis (EAE) induced with proteolipid protein (PLP) 139–151, in which female, but not male, SJL mice show a chronic relapsing-remitting paralysis. Furthermore, dihydrotestosterone (DHT) has been shown to ameliorate the severity of EAE, but the underlying mechanisms of its protective effects are unclear. Using major histocompatibility complex (MHC) class II dextramers for PLP 139-151, we tested the hypothesis that DHT selectively modulates the expansion and functionalities of antigen-specific T cells. Unexpectedly, we noted that DHT induced cell death in antigen-specific, autoreactive T cells, but the effects were not …