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

• 成果类型: Article
• 署名作者: Stinchcombe, Jane C.; Asano, Yukako; Kaufman, Christopher J. G.; Bohlig, Kristin; Peddie, Christopher J.; Collinson, Lucy M.; Nadler, Andre; Griffiths, Gillian M.
• 署名单位: University of Cambridge; Max Planck Society; Francis Crick Institute
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11301
• DOI: 10.1126/science.abp8933
• 发表日期: 2023-05-26
• 页码: 818-823
• 关键词: plasma-membrane; activation; 1; 2-diacylglycerol; lymphocytes; secretion

摘要

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.