Abstract
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, were found to induce varying degrees of myocarditis in immunized mice. One of these, BCKD(k) 111-130, could also induce hepatitis without affecting lungs, kidneys, skeletal muscles, and brain. In immunogenicity testing, all three peptides induced antigen-specific T cell responses, as verified by proliferation assay and/or major histocompatibility complex class II/IA(k) dextramer staining. Finally, the disease-inducing abilities of BCKD(k) peptides were correlated with the production of interferon-γ, and the activated T cells could transfer disease to naive recipients. CONCLUSIONS: The disease induced by BCKD(k) peptides could serve as a useful model to study the autoimmune events of inflammatory heart and liver diseases.