Publications in Scientific Journals:

A. Lipp, K. Juhasz, C. Paar, C. Ogris, P. Eckerstorfer, R. Thuenauer, J. Hesse, B. Nimmervoll, H. Stockinger, G. Schütz, U. Bodenhofer, Z. Balogi, A. Sonnleitner:
"Lck Mediates Signal Transmission from CD59 to the 1 TCR/CD3 Pathway in Jurkat T Cells";
PLoS ONE, 9 (2014), 1; e859341 - e8593412.

English abstract:
The glycosylphosphatidylinositol (GPI)-anchored molecule CD59 has been implicated in the modulation of T cell responses,
but the underlying molecular mechanism of CD59 influencing T cell signaling remained unclear. Here we analyzed Jurkat T
cells stimulated via anti-CD3e- or anti-CD59-coated surfaces, using time-resolved single-cell Ca2+ imaging as a read-out for
stimulation. This analysis revealed a heterogeneous Ca2+ response of the cell population in a stimulus-dependent manner.
Further analysis of T cell receptor (TCR)/CD3 deficient or overexpressing cells showed that CD59-mediated signaling is
strongly dependent on TCR/CD3 surface expression. In protein co-patterning and fluorescence recovery after
photobleaching experiments no direct physical interaction was observed between CD59 and CD3 at the plasma
membrane upon anti-CD59 stimulation. However, siRNA-mediated protein knock-downs of downstream signaling
molecules revealed that the Src family kinase Lck and the adaptor molecule linker of activated T cells (LAT) are essential for
both signaling pathways. Furthermore, flow cytometry measurements showed that knock-down of Lck accelerates CD3 reexpression
at the cell surface after anti-CD59 stimulation similar to what has been observed upon direct TCR/CD3
stimulation. Finally, physically linking Lck to CD3f completely abolished CD59-triggered Ca2+ signaling, while signaling was
still functional upon direct TCR/CD3 stimulation. Altogether, we demonstrate that Lck mediates signal transmission from
CD59 to the TCR/CD3 pathway in Jurkat T cells, and propose that CD59 may act via Lck to modulate T cell responses.

Created from the Publication Database of the Vienna University of Technology.