Skip to main content

T cell signal integration in signalling complexes

Objective

The activation of T lymphocytes is governed by the interaction of specific receptor/ligand pairs on T cell and antigen presenting cell (APC), respectively. The engagement of the T cell receptor (TCR) by peptide/MHC complexes on the APC and the interaction ofCD80/CD86 with their costimulatory or inhibitory receptors CD28 orCTLA-4 on the T cell are among the most important. Combinations of the signals are integrated by the T lymphocyte to mount a distinctive response, such as differentiation, proliferation, anergy, or cell death. T cell stimulation induces the formation of signaling protein complexes in the T cell plasma membrane domain in contact with the APC. This study seeks to investigate the effects of modulated T cell activation on the composition of these T cell signalling complexes and to correlate them with functional parameters of T cell activation. In the presence or absence of costimulatory molecules, various peptide/MHC complexes will be coupled to magnetic beads and used for activation of transgenic murine primary T cells. The formation and composition of these signaling complexes will be studied biochemically and by imaging techniques. In this project, I will enter the field of signal transduction. By working on the project, I will complement my knowledge of cell biological, immunological and biochemical methods with state of the art proteomic analysis and analysis of lipid membranes. The host, Thomas Harder, has developed a novel approach for immunoisolationg TCR-containig membrane domains and associated proteins, which will contribute to the understanding of the integration of TCR-mediated and costimulating signals at the level of signaling complexes and might very well lead to the identification of new components of TCR signalling assemblies. In this project, I will apply this method to the activation of primary T cells isolated from TCR transgenic mice. In my PhD studies, I have extensively studied the activation of murine primary T cells and their effector functions, so the areas of expertise of Thomas Harder and me optimally complement each other.

Topic(s)

Data not available

Call for proposal

Data not available

Coordinator

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Address
South Parks Road
OX1 3RE Oxford
United Kingdom