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SUMMARY:Imaging the First Events in T-Cell Activation - Markus Koerbel\, U
 niversity of Cambridge
DTSTART:20210525T100000Z
DTEND:20210525T103000Z
UID:TALK159604@talks.cam.ac.uk
CONTACT:David Madden
DESCRIPTION:T cells are the drivers of adaptive immunity and detect antige
 ns with unprecedented sensitivity and selectivity. To understand this proc
 ess\, studying the very first interactions of a T cell with an antigen pre
 senting cell (APC) will be key. In order to detect an antigen\, T cells ne
 ed to establish a close contact with a target cell that allows its T-cell 
 receptor to bind the presented antigen. We established a complex “second
  generation” supported lipid bilayer (SLB) model of the APC cell membran
 e to study the influence of adhesion on microvillar contact formation and 
 antigen detection. We demonstrated a fine balance between adhesion and the
  cellular glycocalyx governs T cell activation: Removal of adhesion protei
 ns in the SLB reduced T-cell signaling\, whereas the glycocalyx was necess
 ary to prevent T-cell over-reactivity. To study T-cell-SLB interactions in
  more detail we developed an imaging and analysis pipeline to quantitative
 ly characterize close contact formation with high spatial and temporal res
 olution using TIRF microscopy. We characterised four stages of interaction
 \, and the role of adhesion proteins\, as well as membrane topography\, th
 roughout them. Our study highlights the importance of adhesion in regulati
 ng T-cell function and we could directly visualize the sequence of events 
 underpinning initial T-cell/target contact. Our findings will be important
  for better understanding immune diseases and developing immune therapies.
  Cancer cells\, for example\, can overexpress glycocalyx proteins to preve
 nt an immune response and recently the downregulation of the adhesion prot
 ein CD58 has been identified as a route of immune-evasion by tumors.
LOCATION:via zoom - please contact David Madden for the zoom link
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