Branched chain α-ketoacid dehydrogenase kinase 111-130, a T cell epitope that induces both autoimmune myocarditis and hepatitis in A/J mice. Immun Inflamm Dis 2017 Dec;5(4):421-434
Date
06/10/2017Pubmed ID
28597552Pubmed Central ID
PMC5691315DOI
10.1002/iid3.177Scopus ID
2-s2.0-85034635299 (requires institutional sign-in at Scopus site) 11 CitationsAbstract
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.
Author List
Krishnan B, Massilamany C, Basavalingappa RH, Gangaplara A, Kang G, Li Q, Uzal FA, Strande JL, Delhon GA, Riethoven JJ, Steffen D, Reddy JMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAnimals
Autoantigens
Autoimmune Diseases
Biopsy
Cytokines
Disease Models, Animal
Epitopes, T-Lymphocyte
Hepatitis, Autoimmune
Histocompatibility Antigens Class II
Immunization
Mice
Myocarditis
Peptide Fragments
Protein Kinases
Protein Multimerization
T-Lymphocytes
