Characterization of the CD200 receptor family in mice and humans and their interactions with CD200
Characterization of the CD200 receptor family in mice and humans and their interactions with CD200
复制标题
DOI：
10.4049/jimmunol.171.6.3034
复制
发表时间：
2003-09-15
影响因子：
4.4
通讯作者：
Barclay, AN
中科院分区：
文献类型：
--
作者：
Wright, GJ;Cherwinski, H;Barclay, AN
CD 200（OX 2）是一种广泛分布的细胞表面糖蛋白，与啮齿动物骨髓细胞上表达的结构相关受体（CD 200 R）相互作用，并参与巨噬细胞功能的调节。我们首次报道了人CD 200 R（hCD 200 R）的特性，并定义了其与hCD 200的结合特性。我们还报告了一个与hCD 200 R密切相关的基因，命名为hCD 200 RLa，和四个小鼠CD 200 R相关基因（命名为mCD 200 RLa-d）。CD 200、CD 200 R和CD 200 R相关基因在人类和小鼠中紧密连锁，表明这些基因是通过基因复制产生的。通过定量RT-PCR确定受体基因的分布，并通过一组新的单克隆抗体证实蛋白质表达。小鼠和人CD 200 R的分布相似，巨噬细胞和中性粒细胞的标记最强，但其他白细胞，包括单核细胞、肥大细胞和T淋巴细胞也最强。两个mCD 200受体样家族成员，命名为mCD 200 RLa和mCD 200 RLb，显示与活化衔接蛋白DAP 12配对，表明这些受体将传递强活化信号，而不是通过触发CD 200 R传递的明显抑制信号。尽管与mCD 200 R具有实质性的序列同源性，但mCD 200 RLa和mCD 200 RLb不结合mCD 200，并且目前具有未知的配体。CD 200受体基因家族类似于信号调节蛋白和杀伤性Ig相关受体，其受体家族成员具有潜在的激活和抑制功能，可能在免疫调节和平衡中发挥重要作用。由于CD 200-CD 200 R相互作用的操纵影响啮齿动物疾病模型的结果，因此靶向该途径可能具有治疗效用。免疫学杂志，2003年。
CD200 (OX2) is a broadly distributed cell surface glycoprotein that interacts with a structurally related receptor (CD200R) expressed on rodent myeloid cells and is involved in regulation of macrophage function. We report the first characterization of human CD200R (hCD200R) and define its binding characteristics to hCD200. We also report the identification of a closely related gene to hCD200R, designated hCD200RLa, and four mouse CD200R-related genes (termed mCD200RLa-d). CD200, CD200R, and CD200R-related genes were closely linked in humans and mice, suggesting that these genes arose by gene duplication. The distributions of the receptor genes were determined by quantitative RT-PCR, and protein expression was confirmed by a set of novel mAbs. The distribution of mouse and human CD200R was similar, with strongest labeling of macrophages and neutrophils, but also other leukocytes, including monocytes, mast cells, and T lymphocytes. Two mCD200 receptor-like family members, designated mCD200RLa and mCD200RLb, were shown to pair with the activatory adaptor protein, DAP12, suggesting that these receptors would transmit strong activating signals in contrast to the apparent inhibitory signal delivered by triggering the CD200R. Despite substantial sequence homology with mCD200R, mCD200RLa and mCD200RLb did not bind mCD200, and presently have unknown ligands. The CD200 receptor gene family resembles the signal regulatory proteins and killer Ig-related receptors in having receptor family members with potential activatory and inhibitory functions that may play important roles in immune regulation and balance. Because manipulation of the CD200-CD200R interaction affects the outcome of rodent disease models, targeting of this pathway may have therapeutic utility. The Journal of Immunology, 2003.