Branched chain α‐ketoacid dehydrogenase kinase 111–130, a T cell epitope that induces both autoimmune myocarditis and hepatitis in A/J mice
| Autor: | Krishnan, Bharathi, Massilamany, Chandirasegaran, Basavalingappa, Rakesh H., Gangaplara, Arunakumar, Kang, Guobin, Li, Qingsheng, Uzal, Francisco A., Strande, Jennifer L., Delhon, Gustavo A., Riethoven, Jean‐Jack, Steffen, David, Reddy, Jay |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
mouse model
Biopsy T-Lymphocytes autoreactive T cells Epitopes T-Lymphocyte Autoimmune hepatitis Autoantigens Hepatitis Autoimmune Diseases Epitopes Mice Animals Amino Acid Sequence branched chain α-ketoacid dehydrogenase kinase Original Research Animal branched chain alpha-ketoacid dehydrogenase kinase Histocompatibility Antigens Class II autoimmune myocarditis Peptide Fragments Disease Models Animal Hepatitis Autoimmune Myocarditis branched chain α‐ketoacid dehydrogenase kinase T-Lymphocyte Disease Models Cytokines Immunization Protein Multimerization Protein Kinases Autoimmune |
| Zdroj: | Immunity, Inflammation and Disease Immunity, inflammation and disease, vol 5, iss 4 |
| ISSN: | 2050-4527 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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