Abstract

Genomic restriction fragment polymorphisms for the human EAlpha, EBeta, AAlpha, and ABeta genomic sequences, HLA-DR type, and two dimensional protein electrophoresis pattern for the EAlpha, EBeta, AAlpha, and ABeta polypeptide chains will be correlated for consanguineousmating derived homozygous typing cells of HLA-DR3 and DR4 serotypes, and for a wide variety of homozygous typing cells corresponding to the other established HLA-DR types. Similar analyses will be done on peripheral blood lymphocytes isolated from patients with insulin dependent diabetes mellitus who are HLA-DR3 positive; Graves' disease patients who are HLA-DR3 positive; and insulin dependent diabetes mellitus and rheumatoid arthritis patients who are HLA-DR4 positive. By a combination of restriction fragment polymorphism, serotyping, and two-dimensional protein electrophoresis it is hoped to develop methods for subdividing HLA-DR chromosomes identified by serotyping with HLA-DR alloantisera into subsets or haplotypes which predispose to specific autoimmune diseases. These studies should lead to a much more precise identification of genetic susceptibility to these diseases and to identification of the particular loci which are most important in disease predisposition.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM035635-07
Application #
3288557
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1980-04-01
Project End
1988-03-31
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
7
Fiscal Year
1986
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

Lee, B S; Bell, J I; Rust, N A et al. (1987) Structural and functional variability among DQ beta alleles of DR2 subtypes. Immunogenetics 26:85-91
Bell, J I; Denney Jr, D; Foster, L et al. (1987) Allelic variation in the DR subregion of the human major histocompatibility complex. Proc Natl Acad Sci U S A 84:6234-8
Lee, B S; Rust, N A; McMichael, A J et al. (1987) HLA-DR2 subtypes form an additional supertypic family of DR beta alleles. Proc Natl Acad Sci U S A 84:4591-5
Bell, J I; Steinman, L; Toyka, K et al. (1987) HLA-DQ restriction fragment length polymorphisms in myasthenia gravis. Ann N Y Acad Sci 505:382-7
Bell, J; Rassenti, L; Smoot, S et al. (1986) HLA-DQ beta-chain polymorphism linked to myasthenia gravis. Lancet 1:1058-60
Hardy, D A; Bell, J I; Long, E O et al. (1986) Mapping of the class II region of the human major histocompatibility complex by pulsed-field gel electrophoresis. Nature 323:453-5
McDevitt, H O (1986) The molecular basis of autoimmunity. Clin Res 34:163-75