Allele Specific Prevention of Diabetes Mellitus

McDevitt, Hugh O.

Abstract

1. To use rat monoclonal antibodies to the rat """"""""I-A(u)"""""""" and """"""""I-E(u)"""""""" class II major histocompatibility complex antigens to prevent insulin dependent diabetes mellitus (IDDM) in the BB/Worcester rat. 2. To produce rat monoclonal antibodies to the rat islet cell surface antigen(s) (ICSA) expressed on insulin producing Beta cells. 3. To use monoclonal Alpha-ICSA antibodies to isolate and characterize rat ICSA. 4. To use affinity purified ICSA to prevent IDDM in the BB/Worcester rat. 5. To use purified ICSA to develop a rapid assay for Alpha-ICSA antibody. 6. To clone and sequence the cDNA sequences encoding the variant sub-types of HLA-DR4Beta, HLA-DR3Beta, HLA""""""""DC4""""""""Beta, and HLA-""""""""DC3""""""""Beta.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Type: Research Project (R01)
• Project #: 5R01DK033880-03
• Application #: 3232280
• Study Section: (SSS)
• Project Start: 1984-04-01
• Project End: 1987-03-31
• Budget Start: 1986-04-01
• Budget End: 1987-03-31
• Support Year: 3
• Fiscal Year: 1986

Institution

• Name: Stanford University
• Type: Schools of Medicine
• DUNS #: 800771545
• City: Stanford
• State: CA
• Country: United States
• Zip Code: 94305

Publications

Balasa, B; Krahl, T; Patstone, G et al. (1997) CD40 ligand-CD40 interactions are necessary for the initiation of insulitis and diabetes in nonobese diabetic mice. J Immunol 159:4620-7

Tisch, R; Yang, X D; Liblau, R S et al. (1994) Administering glutamic acid decarboxylase to NOD mice prevents diabetes. J Autoimmun 7:845-50

Yang, X D; Tisch, R; Singer, S M et al. (1994) Effect of tumor necrosis factor alpha on insulin-dependent diabetes mellitus in NOD mice. I. The early development of autoimmunity and the diabetogenic process. J Exp Med 180:995-1004

Yang, X D; Michie, S A; Tisch, R et al. (1994) Cell adhesion molecules: a selective therapeutic target for alleviation of IDDM. J Autoimmun 7:859-64

Yang, X D; Michie, S A; Tisch, R et al. (1994) A predominant role of integrin alpha 4 in the spontaneous development of autoimmune diabetes in nonobese diabetic mice. Proc Natl Acad Sci U S A 91:12604-8

Yang, X D; McDevitt, H O (1994) Role of TNF-alpha in the development of autoimmunity and the pathogenesis of insulin-dependent diabetes mellitus in NOD mice. Circ Shock 43:198-201

Singer, S M; Tisch, R; Yang, X D et al. (1993) An Abd transgene prevents diabetes in nonobese diabetic mice by inducing regulatory T cells. Proc Natl Acad Sci U S A 90:9566-70