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, Chandirasegaran Massilamany, Rakesh H. Basavalingappa, Arunakumar Gangaplara, Guobin Kang, Qingsheng Li, Francisco A Uzal, Jennifer L. Strande, Gustavo A. Delhon, Jean Jack Riethoven, David Steffen, Jay Reddy

Research output: Contribution to journalArticle

5 Scopus citations

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 (BCKDk) that can act as a target autoantigen in the development of autoimmune inflammatory reactions in both heart and liver. Results: We demonstrate that BCKDk protein contains at least nine immunodominant epitopes, three of which, BCKDk 71-90, BCKDk 111-130 and BCKDk 141-160, were found to induce varying degrees of myocarditis in immunized mice. One of these, BCKDk 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/IAk dextramer staining. Finally, the disease-inducing abilities of BCKDk 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 BCKDk peptides could serve as a useful model to study the autoimmune events of inflammatory heart and liver diseases.

Original languageEnglish (US)
Pages (from-to)421-434
Number of pages14
JournalImmunity Inflammation and Disease
Volume5
Issue number4
DOIs
StatePublished - Jan 1 2017

Keywords

  • Autoimmune hepatitis
  • Autoimmune myocarditis
  • Autoreactive T cells
  • Branched chain α-ketoacid dehydrogenase kinase
  • Mouse model

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Krishnan, B., Massilamany, C., Basavalingappa, R. H., Gangaplara, A., Kang, G., Li, Q., Uzal, F. A., Strande, J. L., Delhon, G. A., Riethoven, J. J., Steffen, D., & Reddy, J. (2017). Branched chain α-ketoacid dehydrogenase kinase 111-130, a T cell epitope that induces both autoimmune myocarditis and hepatitis in A/J mice. Immunity Inflammation and Disease, 5(4), 421-434. https://doi.org/10.1002/iid3.177