Quantifying the reduction in accessibility of the inhibitory NK cell receptor Ly49A caused by binding MHC class I proteins in cis
Quantifying the reduction in accessibility of the inhibitory NK cell receptor Ly49A caused by binding MHC class I proteins in cis
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DOI：
10.1002/eji.200636693
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发表时间：
2007-02-01
影响因子：
5.4
通讯作者：
Hoglund, Petter
中科院分区：
文献类型：
--
作者：
Andersson, Katja E.;Williams, Geoffrey S.;Hoglund, Petter
鼠自然杀伤（NK）细胞通过Ly 49受体被靶细胞MHC I类分子抑制。然而，Ly 49受体可以通过与NK细胞膜内的MHC I类配体的顺式相互作用而无法接近靶细胞MHC I类。最近已经证明，MHC I类蛋白从靶细胞转移到NK细胞。在这里，我们建立了转移的MHC I类蛋白的数量与NK细胞表面的Ly 49 A受体的数量成比例。与来自H-2D（d）阴性小鼠的Ly 49 A（+）NK细胞相比，来自表达Ly 49 A配体H-2D（d）的小鼠的Ly 49 A（+）NK细胞显示Ly 49 A可及性降低90%。这种减少是由Ly 49 A的较低表达和Ly 49 A与H-2D（d）在NK细胞表面的顺式相互作用引起的。在表达H-2D（d）的NK细胞上，大约75%的Ly 49 A受体被内源性H-2D（d）顺式占据，只有25%的受体与H-2D（d）反式分子自由相互作用。因此，H-2D（d）配体通过顺式和反式相互作用控制Ly 49 A受体的可及性。
Murine natural killer (NK) cells are inhibited by target cell MHC class I molecules via Ly49 receptors. However, Ly49 receptors can be made inaccessible to target cell MHC class I by a cis interaction with its MHC class I ligand within the NK cell membrane. it has recently been demonstrated that MHC class I proteins transfer from the target cells to the NK cell. Here, we establish that the number of transferred MHC class I proteins is proportional to the number of Ly49A receptors at the NK cell surface. Ly49A(+) NK cells from mice expressing the Ly49A ligand H-2D(d) showed a 90% reduction in Ly49A accessibility compared to Ly49A(+) NK cells from H-2D(d)-negative mice. The reduction was caused both by lower expression of Ly49A and interactions in cis between Ly49A and H-2D(d) at the NK cell surface. Approximately 75% of the Ly49A receptors on H-2D(d)- expressing NK cells were occupied in cis with endogenous H-2D(d) and only 25% were free to interact with H-2D(d) molecules in trans. Thus, H-2D(d) ligands control Ly49A receptor accessibility through interactions both in cis and in trans.