ANTI-IDIOTYPIC AUTOIMMUNITY IN MULTIPLE SCLEROSIS

Project Details

Description

Multiple sclerosis is a chronic demyelinating disease of the human
central nervous system. Genetic, viral and autoimmune factors
are believed to play a role in the pathogenesis of this disorder.
We now propose to investigate the immunoregulatory cells and
mechanisms involved in multiple sclerosis by analyzing the
proliferative and molecular characteristics of T cell clones
specifically reactive against myelin components, in particular, the
basic protein of myelin (MBP). Our hypothesis is that idiotypes
expressed by autoantigen activated T lymphocytes regulate
immune responses through interactions involving anti-idiotypic T
cells and anti-idiotypic antibodies. A defect in this complex
regulatory network may lead to autoimmune diseases such as
multiple sclerosis.

First, the response of the T cell clones to the autoantigen will be
analyzed with respect to the MBP epitope sepcificity and MHC
restriction.

Next, we will study the autologous mixed lymphocyte response in
nultiple sclerosis patients both at a polyclonal and monoclonal
level. The idiotypic nature of anti-MBP T cell lines and clones
will be investigated by determining their ability to induce the
proliferation of resting autologous T cells (anti-idiotypic T cells).
We will then determine the functional nature of the (anti-
idiotypic T cells) generated in the reaction. Likewise, we will
determine whether sera from patients with multiple sclerosis
contain autoantibodies (anti-idiotypic antibodies) which bind anti-
MBP clones. The immune abnormalities associated with multiple
sclerosis that may be the result of defects in the function of anti-
idiotypic autoimmunity will be revealed by these studies.

Finally, molecular characterization of selected anti-MBP clones
will be carried out by the analysis of the T cell receptor alpha and
beta chain gene messages. It is conceivable that a restricted
usage of variable region genes of this receptor exists in the T cell
response to autoantigens. Identification of the varable region
genes used would then provide useful markers for diagnostice and
therapeutic purposes. Taken together, the functional, idiotypic
and genetic characterization of autoreactive T cell clones should
further our understandig of the immune cells and mechanisms
involved in multiple sclerosis, and may provide novel means of
specific immunological treatment.
StatusFinished
Effective start/end date1/1/906/30/93

Funding

  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke

ASJC

  • Immunology

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