Lck Mediates Signal Transmission from CD59 to the TCR/CD3 Pathway in Jurkat T Cells

Anna M Lipp, Kata Juhasz, Christian Paar, Christoph Ogris, Paul Eckerstorfer, Roland Thuenauer, Jan Hesse, Benedikt Nimmervoll, Hannes Stockinger, Gerhard J Schütz, Ulrich Bodenhofer, Zsolt Balogi and Alois Sonnleitner

PLOS ONE, 2014, vol. 9, issue 1, 1-12

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-CD3ε- 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 re-expression at the cell surface after anti-CD59 stimulation similar to what has been observed upon direct TCR/CD3 stimulation. Finally, physically linking Lck to CD3ζ 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.

Date: 2014
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0085934

DOI: 10.1371/journal.pone.0085934

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