Organisation and function of CD4 co-receptor on the surface of T cells at nanoscale

Grant Agency
Grant Agency of the Czech Republic
Year from
Year to
Aim: D4 glycoprotein functions as a co-receptor for the activation of T cells by their main receptor, TCR. The ultimate function of CD4 is the delivery of the proximal tyrosine kinase, Lck, to the receptor-ligand signalling complex. Very little is known about the plasma membrane organisation of CD4 molecules. Using super-resolution microscopy and FRET techniques, we will investigate the changes in localisation of CD4 on resting and activated T cells at nanoscale. To test the importance of various structural motifs for the proper localisation of molecules, CD4 mutants will be expressed and analysed in co-receptor-deficient cells. We will also focus on putative involvement of higher order structures (dimers, dimers-of-dimers and oligomers) in the activation of T cells. Different pools of CD4 molecules involved in TCR signalling and interaction with gp120 during infection by HIV-1 will be mapped. Achieved results should expand our knowledge of CD4 function in T cells with possible effect on improved or novel immunotherapies. Keywords in English: T lymphocytes, receptor, co-receptor, CD4, plasma membrane organisation, super-resolution microscopy, fluorescence techniques, HIV

Mgr. Cebecauer Marek Ph.D.

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