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

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 ?-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-?, 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.

SUBMITTER: Krishnan B 

PROVIDER: S-EPMC5691315 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature