In recent years, studies on T cell recognition of protein antigens have focused on using small peptides to identify immunodominant regions of the protein. These studies have specifically avoided the analysis of structural changes, in the native molecule outside of the antigenic determinant, that may influence T cell recognition. However, the apparent specificity of an immunodominant region may substantially depend on neighboring amino acids that are not directly recognized by the T cells. In this proposal, it is hypothesized that specific amino acid alterations outside the immunodominant region will have an affect on T cell recognition. The Staphylococcal nuclase enzyme, a simple 149 amino acid protein, will be used to study T cell recognition. The immunodominant region of this protein has been identified for H- 2a-restricted T cell clones. Moreover, mutant proteins are available with single amino acid changes that span the length of the molecule. These mutant proteins provide a unique opportunity for studying how structural changes in the molecule influence Staph-nuclease-specific T cell recognition. Specifically, this proposal will determine if these changes have an affect on antigen recognition by either altering that portion of the antigen that is recognized by the T cell receptor or by the Ia molecule.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AI026173-05
Application #
3454633
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1988-04-01
Project End
1993-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
5
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Rush University Medical Center
Department
Type
DUNS #
City
Chicago
State
IL
Country
United States
Zip Code
60612