PLoS Biology：NK细胞敌我识别机制 - 生物研究-生物谷

人体中的NK(Natural killer)细胞可自行识别并杀死发生病变的细胞,英国一项最新研究揭示了这种免疫细胞的敌我识别机制，解答了长期以来人们对其作用机制的疑惑。
英国帝国理工学院的研究人员在新一期美国《公共科学图书馆·生物卷》月刊上报告说，他们使用高速显微镜成像技术，观测到NK细胞对所捕获细胞作出“杀与不杀”抉择的全过程。
报告说，NK细胞表面有许多受体感应器，这些受体分为“激活”和“抑制”两种。当它在人体内捕获一个可疑细胞后，两种受体将传回不同的信号，如果是病变细胞，“激活”信号大大增强，免疫细胞的“杀手本能”将被激活，从而杀死病变细胞；反之，如果捕获的是一个健康细胞，“抑制”信号将占主导地位，该细胞将会被释放。
NK细胞在杀伤靶细胞时不需要抗体参加，也不需要抗原预先致敏。此前人们已经知道它能够在病变细胞和健康细胞之间作出“杀与不杀”的抉择，但并不了解其作用机制。（生物谷Bioon.com）
生物谷推荐原始出处：
PLoS Biol 7(7): e1000159. doi:10.1371/journal.pbio.1000159
Natural Killer Cell Signal Integration Balances Synapse Symmetry and Migration
Fiona J. Culley1¤a, Matthew Johnson1, J. Henry Evans1,Sunil Kumar1, Rupert Crilly1, Juan Casasbuenas1, Tim Schnyder1, MaryamMehrabi1, Mahendra P. Deonarain1, Dmitry S. Ushakov2, Veronique Braud3,Günter Roth4, Roland Brock5¤b, Karsten K?hler1, Daniel M. Davis1*
1 Division of Cell and Molecular Biology, Imperial College London,London, United Kingdom, 2 National Heart and Lung Institute, ImperialCollege London, London, United Kingdom, 3 Institut de PharmacologieMoleculaire et Cellulaire, Centre National de la RechercheScientifique/Université de Nice-Sophia Antipolis, UMR6097, Valbonne,France, 4 Department of Molecular Biology, Interfacultary Institute forCell Biology, University of Tübingen, Tübingen, Germany, 5 Department ofBiochemistry, Nijmegen Centre for Molecular Life Sciences, RadboudUniversity Nijmegen Medical Centre, Nijmegen, The Netherlands
Natural killer (NK) cells discern the health of other cells byrecognising the balance of activating and inhibitory ligands expressedby each target cell. However, how the integration of activating andinhibitory signals relates to formation of the NK cell immune synapseremains a central question in our understanding of NK cell recognition.Here we report that ligation of LFA-1 on NK cells induced asymmetricalcell spreading and migration. In contrast, ligation of the activatingreceptor NKG2D induced symmetrical spreading of ruffled lamellipodiaencompassing a dynamic ring of f-actin, concurrent with polarizationtowards a target cell and a “stop” signal. Ligation of both LFA-1 andNKG2D together resulted in symmetrical spreading but co-ligation ofinhibitory receptors reverted NK cells to an asymmetrical migratoryconfiguration leading to inhibitory synapses being smaller and morerapidly disassembled. Using micropatterned activating and inhibitoryligands, signals were found to be continuously and locally integratedduring spreading. Together, these data demonstrate that NK cells spreadto form large, stable, symmetrical synapses if activating signalsdominate, whereas asymmetrical migratory “kinapses” are favoured ifinhibitory signals dominate. This clarifies how the integration ofactivating and inhibitory receptor signals is translated to anappropriate NK cell response.