Chalifour Anick, Scarpellino Léonardo, Back Jonathan, Brodin Petter, Devèvre Estelle, Gros Frédéric, Lévy Frédéric, Leclercq Georges, Höglund Petter, Beermann Friedrich, Held Werner
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Ch. des Boveresses 155, 1066 Epalinges, Switzerland.
Immunity. 2009 Mar 20;30(3):337-47. doi: 10.1016/j.immuni.2008.12.019.
Natural killer (NK) cells show enhanced functional competence when they express inhibitory receptors specific for inherited major histocompatibility complex class I (MHC-I) molecules. Current models imply that NK cell education requires an interaction of inhibitory receptors with MHC-I expressed on other cells. However, the inhibitory Ly49A receptor can also bind MHC-I ligand on the NK cell itself (in cis). Here we describe a Ly49A variant, which can engage MHC-I expressed on other cells but not in cis. Even though this variant inhibited NK cell effector function, it failed to educate NK cells. The association with MHC-I in cis sequestered wild-type Ly49A, and this was found to relieve NK cells from a suppressive effect of unengaged Ly49A. These data explain how inhibitory MHC-I receptors can facilitate NK cell activation. They dissociate classical inhibitory from educating functions of Ly49A and suggest that cis interaction of Ly49A is necessary for NK cell education.
当自然杀伤（NK）细胞表达针对遗传性主要组织相容性复合体I类（MHC-I）分子的特异性抑制性受体时，其功能能力会增强。当前模型表明，NK细胞的教育需要抑制性受体与其他细胞上表达的MHC-I相互作用。然而，抑制性Ly49A受体也可以与NK细胞自身（顺式）上表达的MHC-I配体结合。在这里，我们描述了一种Ly49A变体，它可以与其他细胞上表达的MHC-I结合，但不能与顺式结合。尽管这种变体抑制了NK细胞的效应功能，但它未能对NK细胞进行教育。顺式中与MHC-I的结合隔离了野生型Ly49A，并且发现这可以使NK细胞免受未结合的Ly49A的抑制作用。这些数据解释了抑制性MHC-I受体如何促进NK细胞的激活。它们将Ly49A的经典抑制功能与教育功能区分开来，并表明Ly49A的顺式相互作用对于NK细胞的教育是必要的。
