The long range goal of the proposed research is to gain a more complete understanding of the molecular basis of the specificity and function of helper T lymphocytes in the initiation and promotion of antibody responses. The proposed experiments are based on recent findings in this laboratory and others that the activation of T cells to soluble protein antigens requires the processing of the native antigen to release a peptide fragment containing the T cell antigenic determinant which is held on the surface of an antigen presenting cell where it is recognized by helper T cell in conjunction with Ia. Once stimulated by its antigenic peptide and Ia T cells secrete nonspecific growth and differentiation factors which can activate resting B cells. B cells are capable of functioning as antigen presenting cells and moreover, B cells which bind an antigen are far more efficient in presenting that antigen to T cells, maximally activating T cells at greatly reduced antigen concentrations as compared to B cells which cannot bind antigen. Thus, under limiting antigen concentrations such as may occur in vivo only antigen specific B cells may be capable of functioning as APC and attracting helper T cells to their surface where growth and differentiation factors are released, providing a mechanism by which nonspecific helper factors can be selectively delivered to antigen-specific B cells. This application represents a continuation of studies of the helper T cell response to the globular protein antigen, cytochrome c. It is intended to define (1) the specificity of T cells for protein antigens focusing on the structural features of proteins and peptides which allow them to function as T cell antigens. (2) the capacity of B cells to interact with helper T cells as antigen presenting cells and as potential targets of immunoregulatory phenomenon, and (3) the repercussion of the T cell's activation by antigen presented by B cells as compared to macrophages or dendritic cells with respect to the induction or prevention of tolerance, the activation of B cells to antibody secretion and the induction of memory B cell differentiation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI018939-05
Application #
3128319
Study Section
Experimental Immunology Study Section (EI)
Project Start
1984-09-30
Project End
1990-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
5
Fiscal Year
1988
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
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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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