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

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.

journal_name

Int J Cardiol

journal_title

International journal of cardiology

authors

Massilamany C,Gangaplara A,Basavalingappa RH,Rajasekaran RA,Khalilzad-Sharghi V,Han Z,Othman S,Steffen D,Reddy J

doi

10.1016/j.ijcard.2015.09.016

subject

Has Abstract

pub_date

2016-01-01 00:00:00

pages

311-21

eissn

0167-5273

issn

1874-1754

pii

S0167-5273(15)30456-3

journal_volume

202

pub_type

杂志文章

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