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Cited by 73Viral Infections and Immunology Researchvaccines and immunoinformatics approachesCardiac Fibrosis and Remodeling

Cryptic Epitope Identified in Rat and Human Cardiac Myosin S2 Region Induces Myocarditis in the Lewis Rat

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Li, Ya, Heuser, Janet S, Kosanke, Stanley D, Hemric, Mark, Cunningham, Madeleine W·2004·The Journal of Immunology
DOI 10.4049/jimmunol.172.5.3225
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Abstract

Myocarditis is a common cause of dilated cardiomyopathy leading to heart failure. Chronic stages of myocarditis may be initiated by autoimmune responses to exposed cardiac Ags after myocyte damage. Cardiac myosin, a heart autoantigen, induced experimental autoimmune myocarditis (EAM) in susceptible animals. Although cardiac myosin-induced myocarditis has been reported in Lewis rats, the main pathogenic epitope has not been identified. Using overlapping synthetic peptides of the S2 region of human cardiac myosin, we identified an amino acid sequence, S2–16 (residues 1052–1076), that induced severe myocarditis in Lewis rats. The myocarditic epitope was localized to a truncated S2–16 peptide (residues 1052–1073), which contained a sequence identical in human and rat cardiac myosin. The S2–16 peptide was not myocarditic for three other strains of rats, in which the lack of myocarditis was accompanied by the absence of strong S2–16-specific lymphocyte responses in vitro. For Lewis rats, S2–16 was characterized as a cryptic epitope of cardiac myosin because it did not recall lymphocyte and Ab responses after immunization with cardiac myosin. Lymphocytes from S2–16 immunized rats recognized not only S2–16, but also peptides in the S2–28 region. Furthermore, peptide S2–28 was the dominant epitope recognized by T cells from cardiac myosin immunized rats. S2–16 was presented by Lewis rat MHC class II molecules, and myocarditis induction was associated with an up-regulation of inflammatory cytokine production. S2–16-induced EAM provides a defined animal model to investigate mechanisms of EAM and modulation of immune responses to prevent autoimmune myocarditis.

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  • Lewis rats immunized with cardiac myosin develop experimental autoimmune myocarditis with multinucleated giant cells, replicating clinical findings in giant cell myocarditis.

    “The immunized rats developed EAM with multinucleated giant cells, replicating clinical findings in giant cell myocarditis.”

    From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [58]

    The section ‘The myocarditis inducing capacity of S2-16 was Lewis strain-specific’ reports multinucleated giant cells in inflammatory lesions and similar infiltrates in rats immunized with human cardiac myosin or its peptides. The introduction describes the Lewis rat model as giant-cell granulomatous EAM, but our copy does not establish that these lesions replicate clinical findings in human giant cell myocarditis. Page numbers were not available in our copy. (LLM, conf=0.84)

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Authors
Li, Y., Heuser, J. S., Kosanke, S. D., Hemric, M., & Cunningham, M. W.
Affiliations
University of Oklahoma Health Sciences Center (US)
Corresponding author
  • Li, Ya
  • Hemric, Mark
ORCID
Cunningham, Madeleine W
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
2004-03-01
Volume
172
Issue
5
Pages
3225-3234
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
DOI
10.4049/jimmunol.172.5.3225
OpenAlex
W1489658392
Cited by
73
References
53
Citations by year
2026: 4 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 3 · 2020: 1 · 2019: 3 · 2018: 2 · 2017: 2 · 2016: 5 · 2015: 1 · 2014: 2 · 2013: 3 · 2012: 3
FWCI
4.37
Type
journal article
Language
en
Open access
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Heart, Lung, and Blood Institute (R56HL056267, R01HL056267, HL-56267)
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
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
Keywords
experimental autoimmune myocarditis, cardiac myosin, cryptic epitopes, Lewis rats, autoantigens, T cell epitopes, MHC class II presentation, inflammatory cytokines, dilated cardiomyopathy, heart failure, autoimmunity
MeSH terms
Adjuvants, Immunologic, Amino Acid Sequence, Animals, Autoantibodies, Autoimmune Diseases, Female, Humans, Immunity, Cellular, Injections, Subcutaneous, Lymphocyte Activation, Major Histocompatibility Complex, Molecular Sequence Data, Myocarditis, Peptide Fragments, Rats, Inbred BB, Rats, Inbred BN, Rats, Inbred F344, Rats, Inbred Lew, Species Specificity, Myosin Subfragments, Immunodominant Epitopes, Antigen Presentation, Cardiac Myosins, Rats

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