It is now well established that T cells play an essential role in the initiation and regulation of antibody responses. The T cells which participate in B cell antibody responses appear to be heterogeneous, complex mixtures of interacting cells which both promote and suppress B cell responses. Consequently, the precise analysis of the specificity of functional helper T cells depends on developing means of analyzing individual T cells in collaboration with B cell populations. We propose to employ two experimental approaches to study individual helper T cells. The first is a limiting dilution analysis which we have successfully employed in this laboratory to analyze antigen-specific helper T cells in collaboration with nonimmune primary B cells. This approach has the advantage of allowing a determination of the frequency and specificity of a helper T cell within an individual T cell repertoire. The second approach we will employ is the establishment of long term cloned helper T cell lines. Although it is difficult to draw general conclusions concerning the T cell repertoire in vivo from cloned T cell lines, this approach offers the enormous advantage of providing a large homogeneous population of T cells for analysis. Used in conjunction, these two protocols are a very powerful tool for the study of the helper T cell repertoire. Employing these two techniques, we will focus our attention on three aspects of the recognition potential of helper T lymphocytes. These are: 1) the T cells' fine specificity for foreign antigenic determinants, 2) the T cell repertoire's recognition of antigen in the context of MHC encoded molecules, and 3) the T cells recognition of antibody. It is hoped that these studies will lead to a better understanding of the precise nature of the T cells' recognition of antigen and B cell surface gene products and the functional potential of the T cells to promote B-cell responses through this recognition.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI018939-02
Application #
3128317
Study Section
Experimental Immunology Study Section (EI)
Project Start
1984-09-30
Project End
1987-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
2
Fiscal Year
1985
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
60208
Eggel, Alexander; Baravalle, Günther; 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

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