Molecular characterization of a novel immune receptor restricted to the monocytic lineage
Molecular characterization of a novel immune receptor restricted to the monocytic lineage
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DOI：
10.4049/jimmunol.173.11.6703
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发表时间：
2004-12-01
影响因子：
4.4
通讯作者：
López-Botet, M
中科院分区：
文献类型：
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作者：
Aguilar, H;Alvarez-Errico, D;López-Botet, M
同源性基本局部比对搜索工具使用本实验室克隆的新型抑制受体（irem1）的序列编码和先前描述的称为CMRF-35的同源序列进行搜索。在此基础上，我们克隆了一个与该家族新成员相对应的全长cDNA，称为骨髓细胞2表达的免疫受体（irem2）。该基因位于染色体17q25.1上，编码205 as的蛋白质，该蛋白质包含一个细胞外区域，包括一个类似igg的区域和一个带正电的氨基酸残基（赖氨酸）的跨膜区域，这预示着它与一个适配器分子的假定关联。事实上，在转染的COS-7细胞中证实了IREM-2和DAP-12之间的相互作用。通过生成特异性抗体并使用骨髓和pbmc，我们观察到IREM-2的表达似乎仅限于单核细胞和骨髓树突状细胞系的成熟造血细胞。体外分化为巨噬细胞或未成熟树突状细胞可下调irem2的表达。与特异性单克隆抗体结合后，irem2在大鼠嗜碱性白血病细胞中与DAP-12一起表达，诱导NFAT转录活性；此外，irem2与单核细胞的结合诱导了tnf - α的产生。综上所述，我们的研究结果表明，irem2是单核细胞谱系中igg超家族的一种新的激活受体。
Homology basic local alignment search tool search was conducted using a sequence encoding for a novel inhibitory receptor (IREM-1) cloned in our laboratory and a previously described homologous sequence termed CMRF-35. On the basis of this information, we cloned a full length cDNA corresponding to a novel member of this family, termed immune receptor expressed by myeloid cells 2 (IREM-2). The gene, located in chromosome 17q25.1, encodes for a protein of 205 as that contains an extracellular region comprising an Ig-like domain and a transmembrane region with a positively charged amino acid residue (lysine), that predicted its putative association with an adapter molecule. Indeed, the interaction between IREM-2 and DAP-12 was confirmed in transfected COS-7 cells. By generating specific Abs and using bone marrow and PBMCs, we observed that IREM-2 expression appeared to be restricted to mature hemopoietic cells of the monocytic and myeloid dendritic cell lineages. In vitro differentiation to macrophages or immature dendritic cells down-regulated IREM-2 expression. Upon engagement with the specific mAbs, IREM-2 expressed in rat basophilic leukemia cells together with DAP-12, induced NFAT transcriptional activity; moreover, IREM-2 engagement on monocytes induced TNF-alpha production. Taken together, our results indicate that IREM-2 is a novel activating receptor of the Ig-superfamily in the monocytic lineage.