*Seminar Series: SCMB Chemistry Seminars
*Location: AIBN Seminar Room (Bldg 75)
*Date: 12/04/2017
*Time: 12:00

Speaker #1 details
*Title of talk: T cell receptor clustering - a mechanism of signal transduction
*Speaker's name: Scientia Professor Katharina Gaus
*Speaker's organisation: EMBL Australia Node in Single Molecule Science and ARC Centre of Excellence in Advanced Molecular Imaging University of New South Wales
Speaker's city/state/country: University of New South Wales
Talk Abstract: Antigen recognition by the T cell receptor (TCR) is a hallmark of the adaptive immune system. When the TCR engages a peptide bound to the restricting major histocompatibility complex molecule (pMHC), it transmits a signal via the associated CD3 complex. How the extracellular antigen recognition event leads to intracellular phosphorylation remains unclear. We use single-molecule localization microscopy and novel analysis to quantify the organization of TCR-CD3 complexes into nanoscale clusters and to distinguish between triggered and non-triggered TCR-CD3 complexes. We found that only TCR-CD3 complexes in dense clusters were phosphorylated and associated with downstream signaling proteins, demonstrating that the molecular density within clusters dictates signal initiation. Both pMHC dose and TCR-pMHC affinity determined the density of TCR-CD3 clusters, which scaled with overall phosphorylation levels (Pageon et al. PNAS 2016). We also developed novel FRET sensors to monitor the rate of receptor clustering (Ma et al. Nat Commun in press) and a sensor that reports membrane charges (Ma et al. Nat Biotech in press). With the latter we examined the role of membrane charges in TCR clustering and signal induction. In summary, we propose a model in which antigen recognition is first translated into receptor clustering and then the density of receptor nanoclusters is translated into signaling. This model may explain how T cells can respond to both the affinity and dose of pMHC molecules with a common signal transduction mechanism.

Scientia Professor Katharina Gaus is Head of the EMBL Australia Node in Single Molecule Science. Her group investigates signal transduction processes in T lymphocytes with advanced fluorescence microscopy approaches.
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Speaker #2 details
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Other Details:
*Host name: Kate Stacey
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*Host email: katryn.stacey@uq.edu.au