Abstract

This proposal has two main areas of investigation: 1) to examine B cell antigen presentation to T cells and 2) to characterize antigen processing by macrophages and B cells. Using functional studies, we will examine the ability of B cells to present antigenic determiants to T cells in a manner similar to macrophages. We will determine if B cell presentation of antigen to T cells is MHC restricted. In addition, we will test the ability of murine lymphoma cells and neonatal B cells to present antigen to T cells. Using functional, biochemical and immunochemical techniques we will study the physical and immunological characteristics of macrophage and B cell antigen processing. Characterization will include studies of antigen degradation and the involement of lysosomes in antigen processing. Using both intact macrophages and B cells and subcellular fractions of these cells we will study the characteristics of immunologically active processed antigen and its possible association with MHC gene products.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI018634-05
Application #
3128062
Study Section
Experimental Immunology Study Section (EI)
Project Start
1982-07-01
Project End
1988-06-30
Budget Start
1986-07-01
Budget End
1988-06-30
Support Year
5
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
National Jewish Health
Department
Type
DUNS #
City
Denver
State
CO
Country
United States
Zip Code
80206

  Publications

Yang, Wen; Grey, Howard M (2003) Study of the mechanism of TCR antagonism using dual-TCR-expressing T cells. J Immunol 170:4532-8
Kimachi, Kazuhiko; Sugie, Katsuji; Grey, Howard M (2003) Effector T cells have a lower ligand affinity threshold for activation than naive T cells. Int Immunol 15:885-92
Huang, Jianyong; Lo, Pei-Fen; Zal, Tomasz et al. (2002) CD28 plays a critical role in the segregation of PKC theta within the immunologic synapse. Proc Natl Acad Sci U S A 99:9369-73
Wang, Rongfang; Wang-Zhu, Yiran; Grey, Howard (2002) Interactions between double positive thymocytes and high affinity ligands presented by cortical epithelial cells generate double negative thymocytes with T cell regulatory activity. Proc Natl Acad Sci U S A 99:2181-6
Huang, J; Sugie, K; La Face, D M et al. (2000) TCR antagonist peptides induce formation of APC-T cell conjugates and activate a Rac signaling pathway. Eur J Immunol 30:50-8
Wang, R; Wang-Zhu, Y; Gabaglia, C R et al. (1999) The stimulation of low-affinity, nontolerized clones by heteroclitic antigen analogues causes the breaking of tolerance established to an immunodominant T cell epitope. J Exp Med 190:983-94
Zugel, U; Wang, R; Shih, G et al. (1998) Termination of peripheral tolerance to a T cell epitope by heteroclitic antigen analogues. J Immunol 161:1705-9
Rogers, P R; Grey, H M; Croft, M (1998) Modulation of naive CD4 T cell activation with altered peptide ligands: the nature of the peptide and presentation in the context of costimulation are critical for a sustained response. J Immunol 160:3698-704
Wang, R; Nelson, A; Kimachi, K et al. (1998) The role of peptides in thymic positive selection of class II major histocompatibility complex-restricted T cells. Proc Natl Acad Sci U S A 95:3804-9
Kimachi, K; Croft, M; Grey, H M (1997) The minimal number of antigen-major histocompatibility complex class II complexes required for activation of naive and primed T cells. Eur J Immunol 27:3310-7

Showing the most recent 10 out of 81 publications