The objective is to gain a detailed insight into the molecular events that are triggered by lymphocyte-recognition of foreign antigens, which lead to the generation of the proper immune responses. The results of these studies will enhance our understanding of the means by which cells of the immune system can deal with viral infections, some virally-induced malignancies organ transplantations and invading microorganisms.
The specific aims of the proposed research are: 1. To study the role of accessory molecules like L3T4, Lyt-2, and LFA-1 in the interactions of T cells with their targets. 2. To identify membrane proteins that, following antigen-recognition, are involved in transmitting transmembrane signals. 3. To prepare new monoclonal antibodies in order to identify new cytoskeletal proteins and membrane proteins which become segregated into the effector-target contact area. 4. To find if T cell and B cell activation involves tyrosine kinase activity, and if so, to identify the phosphorylated proteins. 5. To determine if B cell activation by antigen induces intracellular events like the ones induced during T cell activation. 6. To localize B cell receptors during their interaction with specific T-helper cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI023764-02
Application #
3136143
Study Section
Immunobiology Study Section (IMB)
Project Start
1986-09-01
Project End
1988-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Arts and Sciences
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Schaefer, Brian C; Kappler, John W; Kupfer, Abraham et al. (2004) Complex and dynamic redistribution of NF-kappaB signaling intermediates in response to T cell receptor stimulation. Proc Natl Acad Sci U S A 101:1004-9
Miranda, Luis R; Schaefer, Brian C; Kupfer, Abraham et al. (2002) Cell surface expression of the HIV-1 envelope glycoproteins is directed from intracellular CTLA-4-containing regulated secretory granules. Proc Natl Acad Sci U S A 99:8031-6
Marschner, S; Freiberg, B A; Kupfer, A et al. (1999) Ligation of the CD4 receptor induces activation-independent down-regulation of L-selectin. Proc Natl Acad Sci U S A 96:9763-8
Sperling, A I; Sedy, J R; Manjunath, N et al. (1998) TCR signaling induces selective exclusion of CD43 from the T cell-antigen-presenting cell contact site. J Immunol 161:6459-62
Nagasawa, M; Melamed, I; Kupfer, A et al. (1997) Rapid nuclear translocation and increased activity of cyclin-dependent kinase 6 after T cell activation. J Immunol 158:5146-54
Sinensky, M; Fantle, K; Trujillo, M et al. (1994) The processing pathway of prelamin A. J Cell Sci 107 ( Pt 1):61-7
Kupfer, H; Monks, C R; Kupfer, A (1994) Small splenic B cells that bind to antigen-specific T helper (Th) cells and face the site of cytokine production in the Th cells selectively proliferate: immunofluorescence microscopic studies of Th-B antigen-presenting cell interactions. J Exp Med 179:1507-15
Podack, E R; Kupfer, A (1991) T-cell effector functions: mechanisms for delivery of cytotoxicity and help. Annu Rev Cell Biol 7:479-504
Kupfer, A; Mosmann, T R; Kupfer, H (1991) Polarized expression of cytokines in cell conjugates of helper T cells and splenic B cells. Proc Natl Acad Sci U S A 88:775-9
Kupfer, A; Burn, P; Singer, S J (1990) The PMA-induced specific association of LFA-1 and talin in intact cloned T helper cells. J Mol Cell Immunol 4:317-25

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