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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR041441-03
Application #
2080697
Study Section
Neurology C Study Section (NEUC)
Project Start
1993-05-01
Project End
1997-04-30
Budget Start
1995-05-01
Budget End
1996-04-30
Support Year
3
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229