The long range goal of this program remains to gain an understanding of the specificity of helper T cells for protein antigens. In current terms this translates to an understanding of the T cells recognition of peptides containing the antigenic determinant, associated with class II gene products of the MHC, Ia. Antigenic peptides are produced from native antigens by antigen presenting cells (APC) through a series of steps which at present are poorly understood. These involve the uptake of the antigen into an acidic intracellular compartment, the proteolysis of the antigen releasing peptide fragments and the association of these fragments with Ia for display on the APC surface. The immediate goals of this program are: to define the physiochemical properties of the antigenic fragments initially produced by the APC and of those ultimately associated with Ia; to elucidate the steps involved in binding of peptides to MHC and how this process is regulated; to explore alternative or secondary routes for peptide-Ia association; and to attempt to gain information of the structural properties of the peptide bound to the MHC by two dimensional NMR analysis. These studies will be carried out using a well characterized soluble globular protein antigen cytochrome c for which the T cell antigenic determinant is known in detail and into which appropriate labels can be introduced. The results of these studies should lend, valuable insights into the mechanism(s) underlying the T cell recognition of antigen and be of value in the design and synthesis of T cell antigenic peptides for use as both vaccines and immunoregulatory agents.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI018939-08
Application #
3480990
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1984-09-30
Project End
1995-08-31
Budget Start
1991-09-01
Budget End
1992-08-31
Support Year
8
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Type
Schools of Arts and Sciences
DUNS #
City
Evanston
State
IL
Country
United States
Zip Code
60201
Eggel, Alexander; Baravalle, G√ľnther; Hobi, Gabriel et al. (2014) Accelerated dissociation of IgE-Fc?RI complexes by disruptive inhibitors actively desensitizes allergic effector cells. J Allergy Clin Immunol 133:1709-19.e8
Kim, Beomkyu; Tarchevskaya, Svetlana S; Eggel, Alexander et al. (2012) A time-resolved fluorescence resonance energy transfer assay suitable for high-throughput screening for inhibitors of immunoglobulin E-receptor interactions. Anal Biochem 431:84-9
Wurzburg, Beth A; Kim, Beomkyu; Tarchevskaya, Svetlana S et al. (2012) An engineered disulfide bond reversibly traps the IgE-Fc3-4 in a closed, nonreceptor binding conformation. J Biol Chem 287:36251-7
Kim, Beomkyu; Eggel, Alexander; Tarchevskaya, Svetlana S et al. (2012) Accelerated disassembly of IgE-receptor complexes by a disruptive macromolecular inhibitor. Nature 491:613-7
Wurzburg, Beth A; Jardetzky, Theodore S (2009) Conformational flexibility in immunoglobulin E-Fc 3-4 revealed in multiple crystal forms. J Mol Biol 393:176-90
Cheng, P C; Brown, B K; Song, W et al. (2001) Translocation of the B cell antigen receptor into lipid rafts reveals a novel step in signaling. J Immunol 166:3693-701
Sproul, T W; Malapati, S; Kim, J et al. (2000) Cutting edge: B cell antigen receptor signaling occurs outside lipid rafts in immature B cells. J Immunol 165:6020-3
Wagle, N M; Kim, J H; Pierce, S K (1999) CD19 regulates B cell antigen receptor-mediated MHC class II antigen processing. Vaccine 18:376-86
Cheng, P C; Dykstra, M L; Mitchell, R N et al. (1999) A role for lipid rafts in B cell antigen receptor signaling and antigen targeting. J Exp Med 190:1549-60
Cheng, P C; Steele, C R; Gu, L et al. (1999) MHC class II antigen processing in B cells: accelerated intracellular targeting of antigens. J Immunol 162:7171-80

Showing the most recent 10 out of 48 publications