NEUROMUSCLUAR IMMUNOPATHOLOGY IN EAMG-RESISTANT RATS

Project: Research project

Project Details

Description

Gravis (EAMG), immunological differences between helper T cells from two
inbred rat strains that explain disease susceptibility on the one hand
(in Lewis rats) and disease-resistance on the other hand (in Wistar Furth
rats). The working hypothesis for these studies is that the T cell
compartment in Wistar Furth rats may lack the ability to activate
responsiveness by existing B cells that have the potential to produce
disease-causing antibodies; this quality may be related to a lack of T
cell reactivity toward an epitope(s) contained within the AChR alpha
subunit sequence alpha 100-116 that demonstrates immunodominance in Lewis
rats. Studies will include an evaluation of effects on antibody-mediated
inducible neuromuscular dysfunction by the elimination of this T cell
reactivity in Lewis rats by neonatal tolerance induction and peptide
blocking strategies. Proposed studies will also evaluate the importance
of this deficit in the Wistar Furth T cell specificity repertoire by
comparing the frequency of alpha 100-116 responding cells to the
frequency observed in the Lewis response; included in this evaluation
will be tests for the ability of WF antigen presenting cells to bind and
present the alpha 100-116 peptide that may be responsible for the
inability of Wistar Furth T cells to drive an anti-AChR antibody response
with disease-causing potential.
StatusFinished
Effective start/end date5/1/934/30/98

Funding

  • National Institutes of Health
  • National Institutes of Health: $135,446.00
  • National Institutes of Health: $125,226.00
  • National Institutes of Health

ASJC

  • Medicine(all)

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