Giustiniani Jérôme, Bensussan Armand, Marie-Cardine Anne
Institeut National de la Santé et de la Recherche Médicale Unite 841, Department of Immunology, Université Paris 12, Faculté de Médecine de Créteil, Créteil, France.
J Immunol. 2009 Jan 1;182(1):63-71. doi: 10.4049/jimmunol.182.1.63.
CD160 has been initially identified as a GPI-anchored MHC-class I activating receptor mainly expressed on peripheral blood NK cells. Herein, we report the identification of three additional CD160-related mRNAs generated through alternative splicings of the CD160 gene, among which one encoded a putative CD160 transmembrane isoform (CD160-TM). We first establish that CD160-TM surface expression is highly restricted to NK cells and is activation-dependent. Additionally, we provide evidence that CD160-TM represents a novel activating receptor, as assessed by the increased CD107a NK cell surface mobilization observed upon its engagement. Finally, we demonstrate that the CD160-TM cytoplasmic tail is by itself sufficient to mediate the recruitment of Erk1/2 signaling pathway, and that the initiation of this activation process is dependent on the Src-family kinase p56(lck). The identification of CD160-TM therefore provides new possibilities regarding the role of CD160 isoforms in the regulation of NK cell functions.
CD160最初被鉴定为一种主要在外周血自然杀伤（NK）细胞上表达的糖基磷脂酰肌醇（GPI）锚定的MHC-I类激活受体。在此，我们报告通过CD160基因的可变剪接产生的另外三种与CD160相关的mRNA的鉴定结果，其中一种编码一种推定的CD160跨膜异构体（CD160-TM）。我们首先确定CD160-TM的表面表达高度局限于NK细胞且依赖于激活。此外，我们提供证据表明，通过在其结合时观察到的CD107a在NK细胞表面的动员增加来评估，CD160-TM代表一种新型激活受体。最后，我们证明CD160-TM的细胞质尾巴自身足以介导细胞外信号调节激酶1/2（Erk1/2）信号通路的募集，并且这种激活过程的启动依赖于Src家族激酶p56(lck)。因此，CD160-TM的鉴定为CD160异构体在NK细胞功能调节中的作用提供了新的可能性。
