Abstract

The overall goal of this project is to use autoimmune thyroid disease as a model for determining the underlying pathologic mechanisms in human autoimmune disease. The project has four specific aims that examine cellular aspects of the autoimmune response to thyroid antigens. The first specific aim seeks to determine the antigen specificity and T cell receptor (TCR) structure of intrathyroidal human T cells.
Specific Aim II focuses on the cloning and characterization of TSH receptor specific human T cells. The investigators plan on using a unique system where they transfect EB virus transformed B cells from the patient with the cDNA for the TSH receptor and use these B cells as antigen presenting cells to evolve T cell clones.
Specific Aim III involves an evaluation of the induction of the anergy in T cells responding to thyroid antigens, examining both T cell lines evolved from intrathyroidal tissue and T cell clones produced in Specific Aim II. If resistance to the induction of anergy is seen in these T cells, then the mechanism of this resistance will be evaluated. Finally, Specific Aim IV seeks to identify peptide analogues of TSH receptor amino acid sequences that can be used to inhibit T cell responsiveness to the receptor.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK035764-11
Application #
2391376
Study Section
Endocrinology Study Section (END)
Program Officer
Akolkar, Beena
Project Start
1985-09-01
Project End
1999-03-31
Budget Start
1997-05-10
Budget End
1998-03-31
Support Year
11
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
Mount Sinai School of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
114400633
City
New York
State
NY
Country
United States
Zip Code
10029

  Publications

Levin, Lara; Ban, Yoshiyuki; Concepcion, Erlinda et al. (2004) Analysis of HLA genes in families with autoimmune diabetes and thyroiditis. Hum Immunol 65:640-7
Ban, Yoshiyuki; Concepcion, Erlinda S; Villanueva, Ronald et al. (2004) Analysis of immune regulatory genes in familial and sporadic Graves' disease. J Clin Endocrinol Metab 89:4562-8
Ban, Y; Davies, T F; Greenberg, D A et al. (2004) Arginine at position 74 of the HLA-DR beta1 chain is associated with Graves' disease. Genes Immun 5:203-8
Ciullo, I; Latif, R; Graves, P et al. (2003) Functional assessment of the thyrotropin receptor-beta subunit. Endocrinology 144:3176-81
Tomer, Yaron; Davies, Terry F (2003) Searching for the autoimmune thyroid disease susceptibility genes: from gene mapping to gene function. Endocr Rev 24:694-717
Ban, Y; Davies, T F; Greenberg, D A et al. (2003) Analysis of the CTLA-4, CD28, and inducible costimulator (ICOS) genes in autoimmune thyroid disease. Genes Immun 4:586-93
Villanueva, R; Greenberg, D A; Davies, T F et al. (2003) Sibling recurrence risk in autoimmune thyroid disease. Thyroid 13:761-4
Ando, Takao; Imaizumi, Misa; Graves, Peter et al. (2003) Induction of thyroid-stimulating hormone receptor autoimmunity in hamsters. Endocrinology 144:671-80
Tomer, Yaron; Ban, Yoshiyuki; Concepcion, Erlinda et al. (2003) Common and unique susceptibility loci in Graves and Hashimoto diseases: results of whole-genome screening in a data set of 102 multiplex families. Am J Hum Genet 73:736-47
Tomer, Yaron; Greenberg, David A; Concepcion, Erlinda et al. (2002) Thyroglobulin is a thyroid specific gene for the familial autoimmune thyroid diseases. J Clin Endocrinol Metab 87:404-7

Showing the most recent 10 out of 77 publications