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Biophysics Candidate Seminar – En Cai (Univ California San Francisco)

Date January 30, 2020 @ 4:00 pm - 5:00 pm

How immune cells sense danger: Visualizing T cell antigen detection using high-precision microscopy

The immune system protects us from disease by detecting pathogens and distinguishing them from the body’s own healthy tissue. T cells, a type of immune cells, can detect and destroy infected cells or cancer cells. To do so, T cells scan the surface of target cells through physical contact, looking for “danger signals” — abnormal protein fragments presented on the cell surface, called antigen. T cells can rapidly scan many cells and are very sensitive in detecting antigen presented on them. How T cell solve the classic trade-off between speed and sensitivity in the process of antigen detection is unknown. I used lattice light-sheet microscopy and quantum dot-enabled synaptic contact mapping microscopy to visualize in real-time the dynamic process of T cell antigen detection. I showed that small T cell membrane protrusions, called microvilli, dynamically scan the opposing cell before and during antigen recognition. I found that microvilli survey the majority of opposing surfaces within one minute through anomalous diffusion. Prior to antigen recognition, T cell receptors (TCRs) are non-homogenously distributed into high-density patches on the cell membrane. These patch-like distributions are highly dynamic and are transiently associated with microvilli. Upon antigen recognition, TCR-occupied microvilli are selectively stabilized on the interface of cell-cell contact, known as the immunological synapse. My work defines the efficient cellular search mechanism utilized by T cells and provides a promising strategy to enhance tumor-specific T cell responses in cancer immunotherapy.

Host: John Yelton

Details

Date:
January 30, 2020
Time:
4:00 pm - 5:00 pm
Event Categories:
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Venue

2205 NPB