Immune synapses are large-scale, transient molecular assemblies that serve as platforms for antigen presentation to B and T cells, and target recognition by cytotoxic T cells and natural killer (NK) cells. The formation of an immune synapse is a tightly regulated, stepwise process where the cytoskeleton, cell-surface receptors and signaling proteins rearrange into supramolecular activation clusters (SMACs). Here we use a reductionist system of microcontact-printed artificial immune synapses (AIS) shaped as hallmark SMAC structures to show that the spatial distribution of activating ligands influences the formation, stability and outcome of NK cell synapses. Organizing ligands into donut-shaped AIS resulted in fewer long-lasting, symmetrical synapses compared to dot-shaped AIS. NK cells spreading evenly over either AIS exhibited similar arrangement of the lytic machinery, however degranulation was only possible in regions allowing local signaling. Our results demonstrate that the macroscopic organization of ligands in the synapse can affect its outcome, which could be exploited by target cells as an escape mechanism.

中文翻译：

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NK细胞在建立免疫突触时会在大面积上整合信号，但需要局部刺激以进行脱粒

免疫突触是大规模的瞬时分子装配体，可作为抗原呈递给B和T细胞的平台，并被细胞毒性T细胞和自然杀伤（NK）细胞识别。免疫突触的形成是一个严格调节的逐步过程，其中细胞骨架，细胞表面受体和信号蛋白重新排列成超分子激活簇（SMAC）。在这里，我们使用形状为标志性SMAC结构的微接触印刷人工免疫突触（AIS）的还原论体系来显示活化配体的空间分布会影响NK细胞突触的形成，稳定性和结局。与点状AIS相比，将配体组织成甜甜圈状AIS可以减少持久的对称突触。均匀分布在任一AIS上的NK细胞均表现出相似的裂解机制，但是仅在允许局部信号传导的区域才可能发生脱粒。我们的结果表明，突触中配体的宏观组织可以影响其结果，这可能被靶细胞用作逃逸机制。