Expression and Function of CD300 in NK Cells
Expression and Function of CD300 in NK Cells
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DOI：
10.4049/jimmunol.0903347
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发表时间：
2010-09-01
影响因子：
4.4
通讯作者：
Mandelboim, Ofer
中科院分区：
文献类型：
--
作者：
Lankry, Dikla;Simic, Hrvoje;Mandelboim, Ofer
NK 细胞的杀伤活性受到来自抑制性和激活性 NK 细胞受体（包括 CD300 蛋白家族）的信号的调节。据报道，CD300a 在所有 NK 细胞上表达，并在与未知配体结合后传递抑制信号。 CD300a蛋白含有4个ITIM，与CD300c高度同源。关于这两种受体的功能和分布及其配体的身份知之甚少。在本文中，我们证明 CD300a 确实是人类 NK 细胞表达的抑制性受体，但令人惊讶的是，我们表明并非所有 NK 克隆都以 CD300a 依赖性方式受到抑制。我们使用我们生成的一组 13 种新的抗 CD300a 和 CD300c Ab 证明，CD300a 和 CD300c 在 NK 细胞表面上无法区分。通过突变分析调查，我们发现位于 CD300a 蛋白第三个 ITIM 基序的酪氨酸 267 对于 CD300a 的抑制功能很重要。免疫学杂志，2010，185：2877-2886。
The killing activity of NK cells is regulated by signals derived from inhibitory and activating NK cell receptors, including the CD300 family of proteins. CD300a was reported to be expressed on all NK cells and to deliver an inhibitory signal upon binding to a yet unknown ligand/s. The CD300a protein contains four ITIMs and is highly homologous to CD300c. Little is known about the function and distribution of these two receptors and the identity of their ligand/s. In this article, we show that CD300a is indeed an inhibitory receptor expressed by human NK cells, but surprisingly, we show that not all NK clones are inhibited in a CD300a-dependent manner. We demonstrate, using a panel of 13 new anti-CD300a and CD300c Abs that we generated, that CD300a and CD300c are indistinguishable on the surface of NK cells. Using mutational-analysis survey, we show that tyrosine 267 located in the third ITIM motif of the CD300a protein is important for the inhibitory function of CD300a. The Journal of Immunology, 2010, 185: 2877-2886.