Clathrin controls bidirectional communication between T cells and antigen presenting cells

Audun Kvalvaag1,2, Michael L Dustin2

  • 1Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.

Insights

T cells use dynamic microvilli to survey for antigens. Upon recognition, they employ clathrin-mediated ectocytosis and trans-endocytosis for T cell receptor release and antigen capture.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • T cells utilize dynamic microvilli for antigen surveillance post-extravasation.
  • Upon antigen recognition, T cell microvilli stabilize and form microclusters on antigen-presenting cells.

Purpose of the Study:

  • To explore the functional properties of clathrin machinery in T cell activation.
  • To understand how clathrin regulates distinct membrane transfer modes at the immunological synapse.

Main Methods:

  • Investigated clathrin recruitment by ESCRT-0 component Hrs.
  • Examined the role of epsin-1 in clathrin-mediated trans-endocytosis.
  • Discussed the regulation of clathrin machinery during T cell activation.

Main Results:

  • Clathrin, with ESCRT-0, mediates ectocytosis (CEME) of T cell receptor (TCR)-loaded vesicles within 1-5 minutes.
  • Epsin-1 induces clathrin-mediated trans-endocytosis (CMTE) of TCR-peptide-MHC conjugates after 5-10 minutes.
  • Clathrin machinery controls opposing membrane transfer modes at the immunological synapse.

Conclusions:

  • Clathrin machinery plays a dual role in membrane transfer during T cell activation.
  • The dynamic regulation of clathrin adaptors (Hrs and epsin-1) dictates distinct endocytic and exocytic pathways.

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