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

被引：31
作者：
Stinchcombe, Jane C. [1 ]
Asano, Yukako [1 ]
Kaufman, Christopher J. G. [1 ]
Bohlig, Kristin [2 ]
Peddie, Christopher J. [3 ]
Collinson, Lucy M. [3 ]
Nadler, Andre [2 ]
Griffiths, Gillian M. [1 ]
机构：
[1] Cambridge Inst Med Res, Keith Peters Bldg, Cambridge CB2 0XY, England
[2] Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany
[3] Francis Crick Inst, 1 Midland Rd, London NW1 1AT, England
来源：
SCIENCE | 2023年 / 380卷 / 6647期
基金：
英国医学研究理事会; 英国惠康基金; 欧洲研究理事会;
关键词：
PLASMA-MEMBRANE; ACTIVATION; 1,2-DIACYLGLYCEROL; LYMPHOCYTES; SECRETION;
D O I：
10.1126/science.abp8933
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
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.
引用
收藏
页码：818 / 823
页数：6
相关论文
共 32 条
[1]   Cell Biology of T Cell Receptor Expression and Regulation [J].
Alcover, Andres ;
Alarcon, Balbino ;
Di Bartolo, Vincenzo .
ANNUAL REVIEW OF IMMUNOLOGY, VOL 36, 2018, 36 :103-125
[2]   ACCUMULATION OF 1,2-DIACYLGLYCEROL IN PLASMA-MEMBRANE MAY LEAD TO ECHINOCYTE TRANSFORMATION OF ERYTHROCYTES [J].
ALLAN, D ;
MICHELL, RH .
NATURE, 1975, 258 (5533) :348-349
[3]   RAPID TRANSBILAYER DIFFUSION OF 1,2-DIACYLGLYCEROL AND ITS RELEVANCE TO CONTROL OF MEMBRANE CURVATURE [J].
ALLAN, D ;
THOMAS, P ;
MICHELL, RH .
NATURE, 1978, 276 (5685) :289-290
[4]   TCR activation of human T cells induces the production of exosomes bearing the TCR/CD3/ζ complex [J].
Blanchard, N ;
Lankar, D ;
Faure, F ;
Regnault, A ;
Dumont, C ;
Raposo, G ;
Hivroz, C .
JOURNAL OF IMMUNOLOGY, 2002, 168 (07) :3235-3241
[5]   ACTIVATORS OF PROTEIN KINASE-C DOWN-REGULATE AND PHOSPHORYLATE THE T3/T-CELL ANTIGEN RECEPTOR COMPLEX OF HUMAN LYMPHOCYTES-T [J].
CANTRELL, DA ;
DAVIES, AA ;
CRUMPTON, MJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1985, 82 (23) :8158-8162
[6]   Uni-directional ciliary membrane protein trafficking by a cytoplasmic retrograde IFT motor and ciliary ectosome shedding [J].
Cao, Muqing ;
Ning, Jue ;
Hernandez-Lara, Carmen I. ;
Belzile, Olivier ;
Wang, Qian ;
Dutcher, Susan K. ;
Liu, Yanjie ;
Snell, William J. .
ELIFE, 2015, 4
[7]   Diacylglycerol-dependent binding recruits PKCθ and RasGRP1 C1 domains to specific subcellular localizations in living T lymphocytes [J].
Carrasco, S ;
Merida, I .
MOLECULAR BIOLOGY OF THE CELL, 2004, 15 (06) :2932-2942
[8]   Polarized release of T-cell-receptor-enriched microvesicles at the immunological synapse [J].
Choudhuri, Kaushik ;
Llodra, Jaime ;
Roth, Eric W. ;
Tsai, Jones ;
Gordo, Susana ;
Wucherpfennig, Kai W. ;
Kam, Lance C. ;
Stokes, David L. ;
Dustin, Michael L. .
NATURE, 2014, 507 (7490) :118-+
[9]   TCR Signaling: Mechanisms of Initiation and Propagation [J].
Courtney, Adam H. ;
Lo, Wan-Lin ;
Weiss, Arthur .
TRENDS IN BIOCHEMICAL SCIENCES, 2018, 43 (02) :108-123
[10]   Selective integrin endocytosis is driven by interactions between the integrin α-chain and AP2 [J].
De Franceschi, Nicola ;
Arjonen, Antti ;
Elkhatib, Nadia ;
Denessiouk, Konstantin ;
Wrobel, Antoni G. ;
Wilson, Thomas A. ;
Pouwels, Jeroen ;
Montagnac, Guillaume ;
Owen, David J. ;
Ivaska, Johanna .
NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2016, 23 (02) :172-+
1234