Myocarditis-inducing epitope of myosin binds constitutively and stably to I-Ak on antigen-presenting cells in the heart.
Open accessAbstract
Immune interactions in the heart were studied using a murine model of myosin-induced autoimmune myocarditis. A T cell hybridoma specific for mouse cardiac myosin was generated from A/J mice and used to demonstrate that endogenous myosin/I-Ak complexes are constitutively expressed on antigen-presenting cells in the heart. This T cell hybridoma, Seu.5, was used as a functional probe to identify a myocarditis-inducing epitope of cardiac myosin. Overlapping peptides based on the cardiac myosin heavy chain alpha (myhc alpha) sequences were synthesized and tested for their ability to stimulate Seu.5 T cells. One peptide, myhc alpha (325-357) strongly stimulated the Seu.5 T cells, localizing the epitope to this region of the myhc alpha molecule. Using truncated peptides, the epitope was further localized to residues 334-352. The myhc alpha (334-352) peptide strongly induced myocarditis when administered to A/J mice, which was histologically indistinguishable from that induced by myosin. The myhc alpha (334-352) epitope was present in cardiac myosin and not skeletal muscle myosins, providing a biochemical basis for the cardiac specificity of this autoimmune disease. Induction of myocarditis by this epitope was restricted to the myhc alpha isoform and not the myhc beta isoform, suggesting there may be a difference in the efficiency of generating tolerance to these isoforms of cardiac myosin, which are differentially developmentally regulated. The myhc alpha (334-352) epitope bound to purified I-Ak molecules in a similar manner to other I-Ak-restricted immunogenic epitopes, HEL(48-61) and RNase(43-56). Importantly, the myhc alpha (334-352) epitope was able to bind to I-Ak molecules on the surface of antigen-presenting cells in a stable manner. These findings demonstrate that autoantigenic epitopes can behave in a dominant manner and constitutively bind to class II molecules in the target organ in a similar manner to foreign immunogenic epitopes.
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Immunization with cardiac myosin or its shortened peptide in mice or rats can induce experimental autoimmune myocarditis.
“immunization with cardiac myosin or its shortened peptide in mice or rats could induce the development of experimental autoimmune myocarditis (EAM)”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [65]
The opening summary (p. 1291) says that a shortened cardiac-myosin peptide induced myocarditis in A/J mice, and the Introduction (p. 1291) says that immunization with purified cardiac myosin induced myocarditis in mice. The paper’s experiments are in mice; its reference list names a rat peptide study, but the passages do not establish the claim for rats. (LLM, conf=0.86)
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Heart-specific autoantibodies induced by Coxsackievirus B3: Identification of heart autoantigens
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Impaired thymic tolerance to α-myosin directs autoimmunity to the heart in mice and humans
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Autoimmune Myocarditis, Old Dogs and New Tricks.
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- Authors
- Donermeyer, D. L., Beisel, K. W., Allen, P. M., & Smith, S. C.
- Affiliations
- Washington University in St. Louis (US)
- Venue
- The Journal of experimental medicine
- Publisher
- Rockefeller University Press
- Published
- 1995-11-01
- Volume
- 182
- Issue
- 5
- Pages
- 1291-1300
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2192215
- OpenAlex
- W2137514919
- Cited by
- 140
- References
- 1
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 4 · 2023: 4 · 2022: 3 · 2021: 4 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 5 · 2016: 4 · 2015: 5 · 2014: 10 · 2013: 6 · 2012: 4
- FWCI
- 4.27
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Viral Infections and Immunology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- autoimmune myocarditis, cardiac myosin, epitope mapping, I-Ak, MHC class II, antigen-presenting cells, autoantigens, T cell hybridomas, epitope dominance, myosin isoforms, MHC class II binding, A/J mice
- MeSH terms
- Amino Acid Sequence, Animals, Antigen-Presenting Cells, Histocompatibility Antigens Class II, Autoantigens, Autoimmune Diseases, Hybridomas, Isoenzymes, Mice, Inbred A, Molecular Sequence Data, Myocarditis, Myosins, Peptide Fragments, Protein Binding, T-Lymphocytes, Autoimmunity, Immunodominant Epitopes, Sequence Alignment, Sequence Homology, Amino Acid, Mice
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