Related Experiment Video
Updated: Jul 2, 2025

Spatial and Temporal Control of T Cell Activation Using a Photoactivatable Agonist
Published on: April 25, 2018
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.
Abstract:
In circulation, T cells are spherical with selectin enriched dynamic microvilli protruding from the surface. Following extravasation, these microvilli serve another role, continuously surveying their environment for antigen in the form of peptide-MHC (pMHC) expressed on the surface of antigen presenting cells (APCs). Upon recognition of their cognate pMHC, the microvilli are initially stabilized and then flatten into F-actin dependent microclusters as the T cell spreads over the APC. Within 1-5 min, clathrin is recruited by the ESCRT-0 component Hrs to mediate release of T cell receptor (TCR) loaded vesicles directly from the plasma membrane by clathrin and ESCRT-mediated ectocytosis (CEME). After 5-10 min, Hrs is displaced by the endocytic clathrin adaptor epsin-1 to induce clathrin-mediated trans-endocytosis (CMTE) of TCR-pMHC conjugates. Here we discuss some of the functional properties of the clathrin machinery which enables it to control these topologically opposite modes of membrane transfer at the immunological synapse, and how this might be regulated during T cell activation.
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.
Related Concept Videos
T Cell Activation and Clonal Selection
Naive T cells that have not yet encountered an antigen express two primary CD...
Antigen Presenting Cells
T cells require the help of antigen-presenting cells (APCs), which process foreign antigens into smaller fragments that can be recognized by T cells. These APCs are highly specialized cells that efficiently internalize antigens...
Clathrin Coated Vesicles
Cell-mediated Immune Responses
T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Antigens Involved in Adaptive Immunity
Complete Antigens
Complete antigens possess both immunogenicity and...

