Branched chain α‐ketoacid dehydrogenase kinase 111–130, a T cell epitope that induces both autoimmune myocarditis and hepatitis in A/J mice

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.