Ectocytosis renders TCR signaling self-limiting at the immune synapse


Type
Article
Change log
Authors
Stinchcombe, Jane C  ORCID logo  https://orcid.org/0000-0003-1459-9299
Kaufman, Christopher JG  ORCID logo  https://orcid.org/0000-0003-0040-3531
Bohlig, Kristin 
Peddie, Christopher J  ORCID logo  https://orcid.org/0000-0002-8329-5419
Abstract

Cytotoxic T lymphocytes (CTLs) kill virus-infected and cancer cells via T cell receptor (TCR) recognition. How CTLs terminate signaling and disengage to allow serial killing has remained a mystery. TCR activation triggers membrane specialization within the immune synapse including the production of diacylglycerol (DAG), a lipid that can induce negative membrane curvature. We found that activated TCRs were shed into DAG-enriched ectosomes at the immune synapse rather than internalized via endocytosis, suggesting that DAG may contribute to the outward budding required for ectocytosis. Budding ectosomes were endocytosed directly by target cells, thereby terminating TCR signaling and simultaneously disengaging the CTL from the target cell to allow serial killing. Thus, ectocytosis renders TCR signaling self-limiting.

Description
Keywords
Cell Division, Cell Membrane, Receptors, Antigen, T-Cell, T-Lymphocytes, Cytotoxic, Exocytosis, Immunological Synapses, Cell-Derived Microparticles, Diglycerides
Journal Title
Science
Conference Name
Journal ISSN
0036-8075
1095-9203
Volume Title
Publisher
American Association for the Advancement of Science (AAAS)
Sponsorship
Wellcome Trust (100140/Z/12/Z)
Wellcome Trust (217100/Z/19/Z)