The projects will investigate five different aspects of the role of receptor ligand interactions in the regulation of lymphocyte function. Project 1 will determine the nature and significance of the intracellular and cell surface events that occur during the conjugate formation that follows when the T cell receptor recognizes the antigen peptide-class II MHC and will investigate the nature of the signals (lymphokines and interactions between cell bound molecules) conveyed to the B cell. The location and time of appearance of the relevant molecules and structures will be determined. This studies the cell biology of cell interactions. Project 2 will define the dynamics of T cell-B cell conjugate formation and dissociation and will determine the multiple parameters that regulate these events. The results obtained will be used to develop a model for the way in which various lymphocyte interactions occur in vivo. The approach here is to follow the activities of live cells by light microscopy. Project 3 will investigate the development and function of the subset of T cells bearing gamma/delta chain receptors for antigen in an attempt to understand the physiological significance of these cells. The project will examine the expression and function of T cell receptor genes in transfected cells and transgenic mice. Project 4 will investigate and characterize the various molecules carried in the membranes of activated T cells which are involved in transmitting signals to the B cell. The approach utilizes the techniques of membrane biochemistry to examine isolated components of the system. Project 5 will investigate the role of gangliosides in the modulation of signalling between T cells and B cells and seek to determine the physiological significance of the effects observed. The analysis here is biochemical and will compare the effects in model membranes and whole cell systems.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI023287-08
Application #
3091716
Study Section
Allergy & Clinical Immunology-1 (AITC)
Project Start
1986-05-01
Project End
1994-05-31
Budget Start
1993-06-01
Budget End
1994-05-31
Support Year
8
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Stavnezer, J (2000) Molecular processes that regulate class switching. Curr Top Microbiol Immunol 245:127-68
Rothenberg, B E; Voland, J R (1996) beta2 knockout mice develop parenchymal iron overload: A putative role for class I genes of the major histocompatibility complex in iron metabolism. Proc Natl Acad Sci U S A 93:1529-34
Pal, A; Romain, P L; Singer, N G et al. (1996) Mouse CD6: sequence of cDNA and expression of mRNA. Immunol Lett 49:133-7
Stavnezer, J (1996) Immunoglobulin class switching. Curr Opin Immunol 8:199-205
Stavnezer, J (1996) Antibody class switching. Adv Immunol 61:79-146
Kersh, G J; Hooshmand, F F; Hedrick, S M (1995) Efficient maturation of alpha beta lineage thymocytes to the CD4+CD8+ stage in the absence of TCR-beta rearrangement. J Immunol 154:5706-14
Croft, M; Carter, L; Swain, S L et al. (1994) Generation of polarized antigen-specific CD8 effector populations: reciprocal action of interleukin (IL)-4 and IL-12 in promoting type 2 versus type 1 cytokine profiles. J Exp Med 180:1715-28
Weintraub, B C; Jackson, M R; Hedrick, S M (1994) Gamma delta T cells can recognize nonclassical MHC in the absence of conventional antigenic peptides. J Immunol 153:3051-8
Thor, G; Sepulveda, H; Chada, S et al. (1993) Monoclonal antibody that distinguishes between a phosphorylated, beta 2-microglobulin-associated, and a free, nonphosphorylated, chain of MHC class I. J Immunol 151:211-24
Tonkonogy, S L; Swain, S L (1993) Distinct lymphokine production by CD4+ T cells isolated from mucosal and systemic lymphoid organs. Immunology 80:574-80

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