Recently we described a model of chronic relapsing experimental allergic encephalomyelitis (EAE) induced by myelin basic protein (MBP) or MBP derived peptides in SJL/J (H-2s), PL/J (H-2u) and (SJLxPL)F1 mice. Extension of these studies to C57B1/10Sn (B10) and B10 congenic mice demonstrated clear MHC lingage of disease susceptibility. Mapping studies with B10.A intra H-2 recombinant mice implicated the I-A subregion. H-2s and H-2u mice responded to different encephalitogenic determinats on the MBP mmolecule. Studies with (SJLxPL)F1 mice showed that the response to the two determinants was not expressed co-dominantly. Crosses of B10 (non-responder) with SJL/J or B10.A responder mice led to (B10xSJL)F1 responder and (B10xB10.A)F1 non-responder mice. These findings raise questions which include the basis for the different immunological specificities in H-2s and H-2u mice, the basis for dominance of reactivity to peptide 1-37 in (SJLxPL)F1 mice, and the reason for dominat unresponsiveness in (B10xB10.A)F1 mice. The proposed research will investigate ways in which Ia antigens in homozygous and heterozygous animals affect the immune response against chemically defined epitopes of MBP. The results of these studies may provide an important insight into the relationship of HLA-DR antigens and autoimmunity in man as well as the basic mechanisms of the immune response to an autoantigen.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS010721-12
Application #
3394295
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1976-08-01
Project End
1986-11-30
Budget Start
1985-12-01
Budget End
1986-11-30
Support Year
12
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Emory University
Department
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322