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Molecular imaging analysis of the function of the cytoskeletal regulator DOCK2 during physiological T cell activation

Objective

Recent experiments using twophoton microscopy (2PM) of lymphocytes interacting with dendritic cells (DCs) loaded with cognate peptide – major histocompability complexes (pMHC) have uncovered their dynamic interactions inside lymphoid tissue of small rodents. Depending on the amount of pMHC on the DC surface, motile T cells may either slowly integrate T cell receptor-mediated signals or immediately undergo long-term interactions with DCs. Thus, motility and T cell activation inside lymphoid tissue are closely intertwined.
A key motility-inducing factor is the Rac guanine exchange factor DOCK2. Using 2PM of lymphoid tissue, we previously demonstrated that lymphocytes lacking DOCK2 showed reduced motility. However, it is unclear which intracellular binding partners regulate DOCK2 function in lymphoid cells. Furthermore, the role of DOCK2 expression during interactions between T cells and DCs displaying varying densities of cognate pMHC complexes in vivo has not been explored to date. Here, we propose to carry out an analysis of potential binding partners of DOCK2 recently identified in a yeast-two-hybrid screen. Furthermore, we will perform a 2PM analysis comparing the interaction dynamics of control and DOCK2-deficient T cells with DCs loaded with increasing amounts of cognate pMHC complexes. Our project thus aims to clarify the physiological function of DOCK2 for T cell biology.

Call for proposal

FP7-PEOPLE-2010-RG
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Coordinator

UNIVERSITAET BERN
Address
Hochschulstrasse 6
3012 Bern
Switzerland
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 45 000
Administrative Contact
Marianne Schori (Ms.)