ANTIIDIOTYPIC ANTIBODIES IN MYASTHENIA

Project: Research project

Description

The overall goal of this project is to analyze the autoimmune response
to the acetylcholine receptor (ACHR) in myasthenia gravis (MG) and its
experimental model, experimental autoimmune myasthenia gravis (EAMG), and
to manipulate the expression of the autoantibodies. This analysis will
provide the groundwork for the development of antigen-specific, or idiotope
(Id)-specific, treatments of MG (and other autoimmune diseases as well)
that will be more effective and less toxic than presently available
therapies. A systematic survey of both the T cell and B cell immunogenic
epitopes of the entire AChR in EAMG-susceptible and EAMG-resistant strains
of mice in order to determine the role of the T cell repertoire in the
diversity of the antibody response will be carried out. The T cell
receptor (TcR) V region gene segment usage from T cell clones directed
against the immunogenic T cell epitopes will be determined serologically
and by sequencing cDNA or genomic DNA from these cell clones. The latter
studies will determine whether the restricted TcR gene segment usage
observed in the T-cell-mediated autoimmune disease, experimental allergic
encephalomyelitis, also occurs in the antibody-mediated, T-cell-controlled
autoimmune response in EAMG. Moreover, the effectiveness in blocking EAMG
of anti-clonotypic responses against important TcRs will be assessed.
Also, the role of T cells in the protection from EAMG induced by injection
of, previously developed, anti-Id monoclonal antibodies will be analyzed.
These studies will involve adoptive transfer of T cells from protected
animals to naive animals and determination of TcR gene segment usage in the
protected animals. The proposed experiments will primarily make use of the
pepscanning procedure to survey the AChR epitopes for T cell and B cell
immunogenicity, development of T cell clones and hybridomas, amplification
of cDNA and genomic DNA by polymerase chain reaction, and direct sequencing
of amplified products to determine TcR gene segment usage.
StatusFinished
Effective start/end date7/1/793/31/96

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $152,398.00
  • National Institutes of Health
  • National Institutes of Health

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Anti-Idiotypic Antibodies
Myasthenia Gravis
Autoimmune Experimental Myasthenia Gravis
Cholinergic Receptors
T-Lymphocytes
Antibodies
Autoimmune Diseases
T-Lymphocyte Epitopes
Clone Cells
Hybridomas
Monoclonal Antibodies
Antibody Formation
Genes
Complementary DNA
Immunization
Cytoprotection
Adoptive Transfer
Poisons
Injections
DNA-Directed DNA Polymerase

ASJC

  • Medicine(all)
  • Neuroscience(all)