Integrin-dependent organization and bidirectional vesicular traffic at cytotoxic immune synapses

Autor: Gaia Vasiliver-Shamis, Eric O. Long, Yenan T. Bryceson, Dongfang Liu, Michael L. Dustin, Tobias Meckel
Jazyk: angličtina
Rok vydání: 2016
Předmět:
DOI: 10.1016/j.immuni.2009.05.009
Popis: Cytotoxic lymphocytes kill target cells by releasing the content of secretory lysosomes at the immune synapse. To obtain information on the dynamics and control of cytotoxic immune synapses we imaged human primary, live natural killer cells on lipid bilayers carrying ligands of activation receptors. Formation of an organized synapse was dependent on the presence of the β2 integrin ligand ICAM-1. Ligands of co-activation receptors 2B4 and NKG2D segregated into central and peripheral regions, respectively. Lysosomal protein LAMP-1 that was exocytosed during degranulation accumulated in a large and spatially stable cluster, which overlapped with a site of membrane internalization. Lysosomal compartments reached the plasma membrane at focal points adjacent to centrally accumulated LAMP-1. Imaging of fixed cells revealed that perforin-containing granules were juxtaposed to an intracellular compartment where exocytosed LAMP-1 was retrieved. Thus, cytotoxic immune synapses include a central region of bidirectional vesicular traffic, which is controlled by integrin signaling.
Databáze: OpenAIRE