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Cited by 11Viral Infections and Immunology Researchvaccines and immunoinformatics approachesT-cell and B-cell Immunology

β1-Adrenergic Receptor Contains Multiple IAk and IEk Binding Epitopes That Induce T Cell Responses with Varying Degrees of Autoimmune Myocarditis in A/J Mice

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Basavalingappa, Rakesh H., Massilamany, Chandirasegaran, Krishnan, Bharathi, Gangaplara, Arunakumar, Rajasekaran, Rajkumar A., Afzal, Muhammad Z., Riethoven, Jean-Jack, Strande, Jennifer L. +2 more·2017·Frontiers in Immunology
DOI 10.3389/fimmu.2017.01567PMC PMC5701947
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Abstract

Myocarditis/dilated cardiomyopathy (DCM) patients can develop autoantibodies to various cardiac antigens and one major antigen is β1-adrenergic receptor (β1AR). Previous reports indicate that animals immunized with a β1AR fragment encompassing, 197-222 amino acids for a prolonged period can develop DCM by producing autoantibodies, but existence of T cell epitopes, if any, were unknown. Using A/J mice that are highly susceptible to lymphocytic myocarditis, we have identified β1AR 171-190, β1AR 181-200 and β1AR 211-230 as the major T cell epitopes that bind major histocompatibility complex class II/IAk or IEk alleles, and by creating IAk and IEk dextramers, we demonstrate that the CD4 T cell responses to be antigen-specific. Of note, all the three epitopes were found also to stimulate CD8 T cells suggesting that they can act as common epitopes for both CD4 and CD8 T cells. While, all epitopes induced only mild myocarditis, the disease-incidence was enhanced in animals immunized with all the three peptides together as a cocktail. Although, antigen-sensitized T cells produced mainly interleukin-17A, their transfer into naïve animals yielded no disease. But, steering for T helper 1 response led the T cells reacting to one epitope, β1AR 181-200 to induce severe myocarditis in naïve mice. Finally, we demonstrate that all three β1AR epitopes to be unique for T cells as none of them induced antibody responses. Conversely, animals immunized with a non-T cell activator, β1AR 201-220, an equivalent of β1AR 197-222, had antibodies comprising of all IgG isotypes and IgM except, IgA and IgE. Thus, identification of T cell and B cell epitopes of β1AR may be helpful to determine β1AR-reactive autoimmune responses in various experimental settings in A/J mice.

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  • Other heart autoantigens such as ANT1, β1AR, and SERCA2a could also be targeted by pathogenic T cells implicated in the development of autoimmune myocarditis.

    “Other heart autoantigens such as ANT 1 , β 1AR, and SERCA2a (Ca 2+ adenosine triphosphatase 2a) could also be targeted by pathogenic T cells implicated in the development of autoimmune myocarditis. 71-73”

    From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [72]

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Authors
Basavalingappa, R. H., Massilamany, C., Krishnan, B., Gangaplara, A., Rajasekaran, R. A., Afzal, M. Z., Riethoven, J.-J., Strande, J. L., Steffen, D., & Reddy, J.
Affiliations
  • University of Nebraska–Lincoln (US)
  • Medical College of Wisconsin (US)
ORCID
Venue
Frontiers in Immunology
Publisher
Frontiers Media SA
Published
2017-11-20
Volume
8
Pages
1567-1567
ISSN
1664-3224 (ISSN-L)
DOI
10.3389/fimmu.2017.01567
PMC
PMC5701947
OpenAlex
W2770168337
Cited by
11
References
1
Citations by year
2026: 2 · 2025: 1 · 2024: 2 · 2023: 3 · 2020: 2 · 2019: 1
FWCI
0.64
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Lincoln (University of Nebraska) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Institutes of Health (HL114669)
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
beta1-adrenergic receptor, T cell epitopes, MHC class II binding, autoantibodies, autoimmune myocarditis, dilated cardiomyopathy, CD4+ T cells, CD8+ T cells, IL-17A, T helper 1 response, A/J mice, B-cell epitopes, autoimmunity

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