KIR2DL4 (CD158d), an NK cell-activating receptor with inhibitory potential
KIR2DL4 (CD158d), an NK cell-activating receptor with inhibitory potential
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DOI：
10.4049/jimmunol.168.12.6208
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发表时间：
2002-06-15
影响因子：
4.4
通讯作者：
Long, EO
中科院分区：
文献类型：
--
作者：
Faure, M;Long, EO
KIR 2DL 4（CD 158 d）是杀伤细胞Ig样受体家族的一个不寻常的成员，在所有NK细胞和一些T细胞中表达。KIR 2DL 4激活NK细胞的细胞毒性，尽管在其胞质尾中存在基于免疫受体酪氨酸的抑制基序（ITIM）。这种ITIM对KIR 2DL 4激活功能的作用以及它是否可以提供抑制信号尚不清楚。KIR 2DL 4的突变形式被工程化，其缺乏ITIM中的酪氨酸或跨膜区中激活信号所需的酪氨酸-酪氨酸基序。在重定向裂解测定中测试突变的KIR 2DL 4分子的活性。ITIM不是KIR 2DL 4激活裂解所必需的。KIR 2DL 4的激活信号对另一种含有ITIM的受体的抑制敏感。KIR 2DL 4的活化缺陷突变体抑制活化受体CD 16传递的信号。在用GST融合蛋白的下拉实验中，KIR 2DL 4的酪氨酸磷酸化的胞质尾结合含Src同源2的磷酸酶1和2，抑制性受体KIR 2DL 1的尾也是如此。因此，KIR 2DL 4除了具有激活功能外，还具有抑制潜力。
KIR2DL4 (CD158d) is an unusual member of the killer cell Ig-like receptor family expressed in all NK cells and some T cells. KIR2DL4 activates the cytotoxicity of NK cells, despite the presence of an immunoreceptor tyrosine-based inhibition motif (ITIM) in its cytoplasmic tail. The role of this ITIM on the activating function of KIR2DL4, and whether it can provide inhibitory signals, is not known. Mutated forms of KIR2DL4 were engineered that lacked either the tyrosine in the ITIM or an arginine-tyrosine motif in the transmembrane region that is required for the activation signal. The activity of the mutated KIR2DL4 molecules was tested in a redirected lysis assay. The ITIM was not necessary for activation of lysis by KIR2DL4. The activation signal of KIR2DL4 was sensitive to inhibition by another ITIM-containing receptor. The activation-deficient mutant of KIR2DL4 inhibited the signal delivered by the activating receptor CD16. In pull-down experiments with GST fusion proteins, the tyrosine-phosphorylated cytoplasmic tail of KIR2DL4 bound the Src homology 2-containing phosphatases 1 and 2, as did the tail of the inhibitory receptor KIR2DL1. Therefore, KIR2DL4 has inhibitory potential in addition to its activating function.