Ectocytosis renders T cell receptor signaling self-limiting at the immune synapse

Science. 2023 May 26;380(6647):818-823. doi: 10.1126/science.abp8933. Epub 2023 May 25.


Cytotoxic T lymphocytes (CTLs) kill virus-infected and cancer cells through 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 through 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.

MeSH terms

  • Cell Division
  • Cell Membrane / metabolism
  • Cell-Derived Microparticles / immunology
  • Diglycerides* / metabolism
  • Exocytosis* / immunology
  • Immunological Synapses* / immunology
  • Immunological Synapses* / ultrastructure
  • Receptors, Antigen, T-Cell* / metabolism
  • T-Lymphocytes, Cytotoxic* / immunology


  • Receptors, Antigen, T-Cell
  • Diglycerides