Vortrag: "T cell receptor clustering as a mechanism of signal initiation"
Speaker: Yuanqing Ma (University of New South Wales, Sydney, Australia)
Date: Donnerstag, 16. August 2018, 17:00
Location: Campus FME, Hörsaal der Kinderklinik (Haus 10)
Host: Dr. Werner Zuschratter (Leibniz Institute for Neurobiology Magdeburg)
Further Information: Yuanqing Ma, who will be a guest scientist at the LIN in August 2018 is visiting from the lab of Prof. Katharina Gaus in Sydney. Here is the abstract of his talk:
Antigen recognition by the T cell receptor (TCR) is a hallmark of the adaptive immune system. We have previously used single-molecule localization microscopy (SMLM) to show that antigen binding results in TCR clustering with dense clusters containing the majority of triggered TCRs compared to less dense clusters and TCRs outside clusters (Pageon PNAS 2016). However, whether TCR clustering alone is sufficient to induce the phosphorylation of the TCR-CD3 complex and downstream signalling molecules is not known. To test this TCR trigging mechanism directly and bypass antigen-induce clustering, we engineered an optogenetic version of the TCR that forms reversible protein clusters in a light-controlled manner, by fusing, for example, CD3ζ to the light sensitive domain of photoreceptor cytochrome 2. We showed that light-induced TCR clustering triggered TCR-CD3 phosphorylation, Zap70 membrane recruitment, Ca2+ influx and ERK phosphorylation. Further TCR triggering could be reconstituted in a non-lymphocyte cells where no TCR signalling was observed before light-induced clustering, suggesting that clustering is sufficient to initiate TCR signalling. In conclusion, our data strongly suggest that TCR clustering could be a mechanism of TCR triggering.