人體中的NK(Natural killer)細胞可自行識別并殺死發(fā)生病變的細胞,英國一項最新研究揭示了這種免疫細胞的敵我識別機制，解答了長(cháng)期以來(lái)人們對其作用機制的疑惑。
英國帝國理工學(xué)院的研究人員在新一期美國《公共科學(xué)圖書(shū)館·生物卷》月刊上報告說(shuō)，他們使用高速顯微鏡成像技術(shù)，觀(guān)測到NK細胞對所捕獲細胞作出“殺與不殺”抉擇的全過(guò)程。
報告說(shuō)，NK細胞表面有許多受體感應器，這些受體分為“激活”和“抑制”兩種。當它在人體內捕獲一個(gè)可疑細胞后，兩種受體將傳回不同的信號，如果是病變細胞，“激活”信號大大增強，免疫細胞的“殺手本能”將被激活，從而殺死病變細胞；反之，如果捕獲的是一個(gè)健康細胞，“抑制”信號將占主導地位，該細胞將會(huì )被釋放。
NK細胞在殺傷靶細胞時(shí)不需要抗體參加，也不需要抗原預先致敏。此前人們已經(jīng)知道它能夠在病變細胞和健康細胞之間作出“殺與不殺”的抉擇，但并不了解其作用機制。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
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