Mouse strains with mutations in major histocompatibility loci have proved extremely useful for genetic and immunologic investigations of MHC antigens. The first mutation (bm12) discovered in an I-A gene has already provided several new insights into structural and functional properties of Ia molecules, including direct genetic evidence that Ia antigens are identical with the cell surface molecules which regulate the immune response (the putative Ir gene products). The further studies using bm12 mice proposed in this application should allow precise correlations between structural changes in Ia molecules and resulting serologic and functional changes. The T-cell recognition and humoral responses to restricted Ia antigenic determinants will be studied using cloned T-cell lines, monoclonal and alloantisera, and antiidiotypic reagents. Immune functions, known to involve Ia, such as response to insulins of various species, haplotype-specific suppression and skin graft enhancement, will be investigated using bm12 mice. Using similar approaches, newly discovered Ia mutants (variants) will be serologically, chemically and functionally characterized, and each of these strains should elucidate new insights into the immunologic role of individual I region gene products.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI019993-03
Application #
3129454
Study Section
Immunobiology Study Section (IMB)
Project Start
1983-04-01
Project End
1988-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Spinella, D G; Hansen, T H; Walsh, W D et al. (1987) Receptor diversity of insulin-specific T cell lines from C57BL (H-2b) mice. J Immunol 138:3991-5
Hansen, T H; Tse, H Y (1987) Insights into immune-response gene function using an Ia mutant mouse strain. Crit Rev Immunol 7:169-91
Hansen, T H; Walsh, W D; Rubocki, R J et al. (1986) Responses of B6.C-H-2bm12 to heterologous insulins show no correlation with the putative gene conversion but define Iabm12 as functionally unique. J Mol Cell Immunol 2:359-68
Tse, H Y; Kanamori, S; Walsh, W D et al. (1985) The murine bm12 gene conversion provides evidence that T cells recognize predominantly Ia conformation. Proc Natl Acad Sci U S A 82:7058-62
Melino, M R; Epstein, S L; Tse, H Y et al. (1985) Characterization of a dominant anti-Ia idiotype using the IA mutant mouse strain B6.C-H-2bm12. Mol Immunol 22:417-26
Hansen, T H; Koprak, S L; Wormstall, E M et al. (1985) Long-term passive enhancement of allogeneic skin grafts with monoclonal antibodies. J Immunogenet 12:167-73