AUTOIMMUNE DETERMINANTS OF HUMAN CARDIAC MYOSIN

  • Cunningham, Madeleine W. (PI)
  • Cunningham, Madeleine W. (PI)
  • Cooper, Leslie T Jr. (PI)
  • Kinney, Lea (PI)
  • Kinney, Lea (PI)
  • Kinney, Lea (PI)
  • Kinney, Lea (PI)

Project: Research project

Project Details

Description

DESCRIPTION (Adapted from Investigator's abstract): Myocarditis is a
sequela of viral or bacterial infections in humans and occurs in susceptible
animal strains following coxsackievirus infection or immunization with
cardiac myosin. In some instances, myocarditis may be due to molecular
mimicry between an infectious pathogen and the host autoantigen cardiac
myosin. Myocarditis may result from exposure of the host to mimicking
epitopes which may break tolerance against cardiac myosin. Although cardiac
myosin is the known autoantigen which can induce myocarditis in animals, the
molecular basis of the pathogenesis of the disease in humans remains
unknown. In addition, there are few studies in humans which identify the
immunological epitopes defining the disease. The goal of the proposed work
is to define the autoimmune response to human cardiac myosin in animal
models of myocarditis and in humans with myocarditis and to test the
hypothesis that the anti-myosin antibodies and T-cells in the disease are
crossreactive with viral or bacterial epitopes. For these reasons, the
investigators have chosen to explore the following objects: 1) To produce
human anti-myosin monoclonal antibodies (Mabs) from patients with
myocarditis and investigate the Mabs reactivity with human cardiac myosin
and its fragments and synthetic peptides, streptococcal M protein and
coxsackieviral proteins and peptides, and to investigate mAb cytotoxicity
against heart cells in culture; 2) To investigate the T-cell response in
myocarditis patients to human cardiac myosin, fragments and synthetic
peptides, streptococcal M Protein and coxsackieviral peptides, including
production of human cardiac myosin response T-cell clones; 3)a) To determine
the specificity of the heart specific infiltrating T-cells/lines/clones from
hearts in animals models (Lewis rats and A/J and MRL mice) of myocarditis.
T-cell lines/clones will be tested for responsiveness to fragments of human
cardiac myosin, streptococcal M protein, and coxsackieviral proteins and
peptides and will be compared with the specificities of the human T-cell
response in myocarditis, b) to study pathogenic peptides of myosin,
coxsackievirus or streptococcal M protein to determine their ability to
produce tolerance against coxsackieviral or myosin-induced myocarditis.
StatusFinished
Effective start/end date8/1/978/31/16

Funding

  • National Heart, Lung, and Blood Institute: $433,524.00
  • National Heart, Lung, and Blood Institute: $515,955.00

ASJC

  • Medicine(all)

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