The proposed research will seek to prove that specific immune reactions induced by an enriched sarcolemma antigen (SRA) produce myofiber lesions which may lead to congestive cardiomyopathy. The research plan calls for three phased strategies: 1) enrichment of SRA by sodium dodecyl sulfate solubilization, Sephadex chromatography and Western Blot electrophoresis. Identification of the relevant polypeptides will be done by 125I-/35S - labeling techniques, fluorography, immunoprecipitation and production of monoclonal anti-SRA; 2) inhibition of development of immune cardiomyopathy by (a) immunization with T - lymphoblasts to SRA and (b) treatment with monoclonal anti - idiotypic SRA. Computerized image analysis of the myofiber lesions and 51Cr - release assay of syngeneic myofibers will assay effectiveness of inhibition of cardiac disease; 3) the role of putative disordered immunoregulation will be characterized by measuring possible (a) loss of T - cell suppressor function, (b) increased T - cell inducer responses, and (c) B - cell production of anti - T cell autoantibodies in mice that develop immune cardiomyopathy. This will be done by quantitating the efficiency of graded numbers of greatly purified lymphoid populations of B - cells, Ly - 1 cells, Ly - 2,3 cells, and Ly - 1,2,3 cells in the in vitro production of syngeneic myofiber cytotoxicity. The proposed research will provide the data base of the role of the antigenic determinants in SRA in the experimental production of cardiomyopathy.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL034221-02
Application #
3346968
Study Section
Cardiovascular and Pulmonary Research B Study Section (CVB)
Project Start
1986-08-01
Project End
1989-07-31
Budget Start
1987-08-01
Budget End
1988-07-31
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Weill Medical College of Cornell University
Department
Type
Schools of Medicine
DUNS #
201373169
City
New York
State
NY
Country
United States
Zip Code
10065
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