Localization of CD8 T cell epitope within cardiac myosin heavy chain-α334-352 that induces autoimmune myocarditis in A/J mice

Chandirasegaran Massilamany, Arunakumar Gangaplara, Rakesh H. Basavalingappa, Rajkumar A. Rajasekaran, Vahid Khalilzad-Sharghi, Zhongji Han, Shadi Othman, David Steffen, Jay Reddy

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: Cardiac myosin heavy chain-α (Myhc), an intracellular protein expressed in the cardiomyocytes, has been identified as a major autoantigen in cardiac autoimmunity. In our studies with Myhc334-352-induced experimental autoimmune myocarditis in A/J mice (H-2ª), we discovered that Myhc334-352, supposedly a CD4 T cell epitope, also induced antigen-specific CD8 T cells that transfer disease to naive animals. Methods and results: In our efforts to identify the CD8 T cell determinants, we localized Myhc338-348 within the full length-Myhc334-352, leading to four key findings. (1) By acting as a dual epitope, Myhc338-348 induces both CD4 and CD8 T cell responses. (2) In a major histocompatibility complex (MHC) class I-stabilization assay, Myhc338-348 was found to bind H-2Dd - but not H-2Kk or H-2Ld - alleles. (3) The CD8 T cell response induced by Myhc338-348 was antigen-specific, as evaluated by MHC class I/H-2Dd dextramer staining. The antigen-sensitized T cells predominantly produced interferon-γ, the critical cytokine of effector cytotoxic T lymphocytes. (4) Myhc338-348 was found to induce myocarditis in immunized animals as determined by histology and magnetic resonance microscopy imaging. Conclusions: Our data provide new insights as to how different immune cells can recognize the same antigen and inflict damage through different mechanisms.

Original languageEnglish (US)
Pages (from-to)311-321
Number of pages11
JournalInternational Journal of Cardiology
Volume202
DOIs
StatePublished - Jan 1 2016

Fingerprint

Cardiac Myosins
T-Lymphocyte Epitopes
Myosin Heavy Chains
Myocarditis
T-Lymphocytes
Major Histocompatibility Complex
Antigens
CD8 Antigens
Autoantigens
Cytotoxic T-Lymphocytes
Autoimmunity
Cardiac Myocytes
Interferons
Epitopes
Microscopy
Histology
Alleles
Magnetic Resonance Imaging
Staining and Labeling
Cytokines

Keywords

  • Autoimmunity
  • CD8 T cells
  • Cardiac myosin
  • MHC class I dextramers
  • Myocarditis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Localization of CD8 T cell epitope within cardiac myosin heavy chain-α334-352 that induces autoimmune myocarditis in A/J mice. / Massilamany, Chandirasegaran; Gangaplara, Arunakumar; Basavalingappa, Rakesh H.; Rajasekaran, Rajkumar A.; Khalilzad-Sharghi, Vahid; Han, Zhongji; Othman, Shadi; Steffen, David; Reddy, Jay.

In: International Journal of Cardiology, Vol. 202, 01.01.2016, p. 311-321.

Research output: Contribution to journalArticle

Massilamany, Chandirasegaran ; Gangaplara, Arunakumar ; Basavalingappa, Rakesh H. ; Rajasekaran, Rajkumar A. ; Khalilzad-Sharghi, Vahid ; Han, Zhongji ; Othman, Shadi ; Steffen, David ; Reddy, Jay. / Localization of CD8 T cell epitope within cardiac myosin heavy chain-α334-352 that induces autoimmune myocarditis in A/J mice. In: International Journal of Cardiology. 2016 ; Vol. 202. pp. 311-321.
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abstract = "Background: Cardiac myosin heavy chain-α (Myhc), an intracellular protein expressed in the cardiomyocytes, has been identified as a major autoantigen in cardiac autoimmunity. In our studies with Myhc334-352-induced experimental autoimmune myocarditis in A/J mice (H-2ª), we discovered that Myhc334-352, supposedly a CD4 T cell epitope, also induced antigen-specific CD8 T cells that transfer disease to naive animals. Methods and results: In our efforts to identify the CD8 T cell determinants, we localized Myhc338-348 within the full length-Myhc334-352, leading to four key findings. (1) By acting as a dual epitope, Myhc338-348 induces both CD4 and CD8 T cell responses. (2) In a major histocompatibility complex (MHC) class I-stabilization assay, Myhc338-348 was found to bind H-2Dd - but not H-2Kk or H-2Ld - alleles. (3) The CD8 T cell response induced by Myhc338-348 was antigen-specific, as evaluated by MHC class I/H-2Dd dextramer staining. The antigen-sensitized T cells predominantly produced interferon-γ, the critical cytokine of effector cytotoxic T lymphocytes. (4) Myhc338-348 was found to induce myocarditis in immunized animals as determined by histology and magnetic resonance microscopy imaging. Conclusions: Our data provide new insights as to how different immune cells can recognize the same antigen and inflict damage through different mechanisms.",
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AU - Gangaplara, Arunakumar

AU - Basavalingappa, Rakesh H.

AU - Rajasekaran, Rajkumar A.

AU - Khalilzad-Sharghi, Vahid

AU - Han, Zhongji

AU - Othman, Shadi

AU - Steffen, David

AU - Reddy, Jay

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N2 - Background: Cardiac myosin heavy chain-α (Myhc), an intracellular protein expressed in the cardiomyocytes, has been identified as a major autoantigen in cardiac autoimmunity. In our studies with Myhc334-352-induced experimental autoimmune myocarditis in A/J mice (H-2ª), we discovered that Myhc334-352, supposedly a CD4 T cell epitope, also induced antigen-specific CD8 T cells that transfer disease to naive animals. Methods and results: In our efforts to identify the CD8 T cell determinants, we localized Myhc338-348 within the full length-Myhc334-352, leading to four key findings. (1) By acting as a dual epitope, Myhc338-348 induces both CD4 and CD8 T cell responses. (2) In a major histocompatibility complex (MHC) class I-stabilization assay, Myhc338-348 was found to bind H-2Dd - but not H-2Kk or H-2Ld - alleles. (3) The CD8 T cell response induced by Myhc338-348 was antigen-specific, as evaluated by MHC class I/H-2Dd dextramer staining. The antigen-sensitized T cells predominantly produced interferon-γ, the critical cytokine of effector cytotoxic T lymphocytes. (4) Myhc338-348 was found to induce myocarditis in immunized animals as determined by histology and magnetic resonance microscopy imaging. Conclusions: Our data provide new insights as to how different immune cells can recognize the same antigen and inflict damage through different mechanisms.

AB - Background: Cardiac myosin heavy chain-α (Myhc), an intracellular protein expressed in the cardiomyocytes, has been identified as a major autoantigen in cardiac autoimmunity. In our studies with Myhc334-352-induced experimental autoimmune myocarditis in A/J mice (H-2ª), we discovered that Myhc334-352, supposedly a CD4 T cell epitope, also induced antigen-specific CD8 T cells that transfer disease to naive animals. Methods and results: In our efforts to identify the CD8 T cell determinants, we localized Myhc338-348 within the full length-Myhc334-352, leading to four key findings. (1) By acting as a dual epitope, Myhc338-348 induces both CD4 and CD8 T cell responses. (2) In a major histocompatibility complex (MHC) class I-stabilization assay, Myhc338-348 was found to bind H-2Dd - but not H-2Kk or H-2Ld - alleles. (3) The CD8 T cell response induced by Myhc338-348 was antigen-specific, as evaluated by MHC class I/H-2Dd dextramer staining. The antigen-sensitized T cells predominantly produced interferon-γ, the critical cytokine of effector cytotoxic T lymphocytes. (4) Myhc338-348 was found to induce myocarditis in immunized animals as determined by histology and magnetic resonance microscopy imaging. Conclusions: Our data provide new insights as to how different immune cells can recognize the same antigen and inflict damage through different mechanisms.

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