Ligand dimensions are important in controlling NK-cell responses.
Ligand dimensions are important in controlling NK-cell responses.
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DOI：
10.1002/eji.201040335
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发表时间：
2010-07
影响因子：
5.4
通讯作者：
Gould, Keith G.
中科院分区：
文献类型：
--
作者：
Brzostek, Joanna;Chai, Jian-Guo;Gebhardt, Friedemann;Busch, Dirk H.;Zhao, Rui;van der Merwe, P. Anton;Gould, Keith G.
细胞-细胞接触界面上的大小依赖性蛋白质分离已被认为是调节淋巴细胞功能的关键。我们研究了配体尺寸在调节小鼠NK细胞活化和抑制中的作用。在RMA细胞系中生成并稳定表达延长形式的H60 a（一种小鼠NKG 2D配体）。表达正常大小H60 a的RMA细胞被新鲜分离的和IL-2刺激的C57 BL/6小鼠来源的NK细胞有效裂解;然而，裂解水平随着H60 a配体大小的增加而降低。重要的是，H60 a延长不影响NKG 2D结合，如通过可溶性NKG 2D四聚体染色和通过检查NK细胞靶细胞缀合物形成所确定的。CHO细胞在活化来自C57 BL/6小鼠的NK细胞方面是有效的，并且H-2Kb（小鼠抑制性受体Ly 49 C的配体）的单链形式的表达强烈抑制Ly 49 C/I阳性NK细胞的这种活化。H-2Kb的延长导致NK细胞对裂解和IFN-γ产生的抑制降低。这些结果表明，小的配体尺寸是重要的NK细胞的激活和抑制，并建议有不同类型的淋巴细胞受体触发机制之间的共享功能。
Size-dependent protein segregation at the cell–cell contact interface has been suggested to be critical for regulation of lymphocyte function. We investigated the role of ligand dimensions in regulation of mouse NK-cell activation and inhibition. Elongated forms of H60a, a mouse NKG2D ligand, were generated and expressed stably in the RMA cell line. RMA cells expressing the normal size H60a were lysed efficiently by both freshly isolated and IL-2 stimulated C57BL/6 mouse-derived NK cells; however the level of lysis decreased as the H60a ligand size increased. Importantly, H60a elongation did not affect NKG2D binding, as determined by soluble NKG2D tetramer staining, and by examining NK-cell target cell conjugate formation. CHO cells are efficient at activating NK cells from C57BL/6 mice, and expression of a single chain form of H-2Kb, a ligand for the mouse inhibitory receptor Ly49C, strongly inhibited such activation of Ly49C/I positive NK cells. Elongation of H-2Kb resulted in decreased inhibition of both lysis and IFN-γ production by NK cells. These results establish that small ligand dimensions are important for both NK-cell activation and inhibition, and suggest that there are shared features between the mechanisms of receptor triggering on different types of lymphocytes.
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