Abstract

The research projects currently under way in this laboratory comprise a broad program designed to probe the role of class II MHC molecules in immunity and self-tolerance; in the failure of self-tolerance, and to develop means to potentiate or to block the action of MHC molecules in mediating the immune response to foreign antigens, self antigens and self-tumor antigens. The knowledge of structure-function relationships of MHC class II molecules gained in these experiments will then be applied to several animal disease models and human disease states. Parallel experiments are designed to determine the immuno-regulatory role of lymphokines, which directly or indirectly regulate the level of expression and site of expression of class II MHC molecules. A separate set of experiments will expand our on-going study of MHC class II allelic polymorphism by searching for class II polymorphic sequences in species which have diverged from the human evolutionary line five million years ago (chimpanzees) and approximately 20 million years ago (cynomolgus monkeys). These experiments should permit an evaluation of the evolutionary conservation of class II MHC polymorphic sequences critical for the function of these molecules in regulating the immune response.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Unknown (R35)
Project #
1R35CA049734-01
Application #
3479731
Study Section
(SRC)
Project Start
1989-09-08
Project End
1996-08-31
Budget Start
1989-09-08
Budget End
1990-08-31
Support Year
1
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

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

  Publications

Michie, S A; Sytwu, H K; McDevitt, J O et al. (1998) The roles of alpha 4-integrins in the development of insulin-dependent diabetes mellitus. Curr Top Microbiol Immunol 231:65-83
Yang, X D; Sytwu, H K; McDevitt, H O et al. (1997) Involvement of beta 7 integrin and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in the development of diabetes in obese diabetic mice. Diabetes 46:1542-7
Sytwu, H K; Liblau, R S; McDevitt, H O (1996) The roles of Fas/APO-1 (CD95) and TNF in antigen-induced programmed cell death in T cell receptor transgenic mice. Immunity 5:17-30
Fugger, L; Rothbard, J B; Sonderstrup-McDevitt, G (1996) Specificity of an HLA-DRB1*0401-restricted T cell response to type II collagen. Eur J Immunol 26:928-33
McDermott, M; Kastner, D L; Holloman, J D et al. (1995) The role of T cell receptor beta chain genes in susceptibility to rheumatoid arthritis. Arthritis Rheum 38:91-5
McDermott, M; Hsu, C; Molloy, M G et al. (1995) Non-linkage of a T-cell receptor gamma chain microsatellite (D7S485) to rheumatoid arthritis in multiplex families. J Autoimmun 8:131-8
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
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
Fugger, L; Michie, S A; Rulifson, I et al. (1994) Expression of HLA-DR4 and human CD4 transgenes in mice determines the variable region beta-chain T-cell repertoire and mediates an HLA-DR-restricted immune response. Proc Natl Acad Sci U S A 91:6151-5

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