Structure and expression of human IgG FcRII(CD32). Functional heterogeneity is encoded by the alternatively spliced products of multiple genes.
Structure and expression of human IgG FcRII(CD32). Functional heterogeneity is encoded by the alternatively spliced products of multiple genes.
复制标题
DOI：
10.1084/jem.170.4.1369
复制
发表时间：
1989-10-01
期刊：
影响因子：
--
通讯作者：
Ravetch JV
中科院分区：
文献类型：
--
作者：
Brooks DG;Qiu WQ;Luster AD;Ravetch JV
人免疫球蛋白低亲和力受体FcRII(CD32)的结构异质性已经通过分离、鉴定和表达来自髓系和淋巴系RNA的cDNA克隆来阐明。这些克隆预测的氨基酸序列与具有单一跨膜结构域的完整膜糖蛋白一致。胞外区显示出与其他Fc、Gamma Rs和Ig超基因家族成员的序列同源性。至少有三个基因(Fc Gamma RIa、IIa‘和Fc Gamma RIIb)编码这些转录本，这些转录本显示出高度相关的胞外和膜跨结构域。IIa/IIa‘在胞质结构域上与IIb有很大不同。IIb基因的选择性剪接在预测蛋白质的NH2-和COOH-末端结构域中产生进一步的异质性。与这些分子的小鼠同源基因进行比较，发现其中一个基因Fc-Gamma RIIb的产物在初级序列、剪接模式和组织分布上与小鼠β基因高度保守。相反，IIa‘的序列表明了它与类β基因的关系，突变产生了一个新的细胞质结构域，而IIa是α和类β基因的嵌合体。通过转染法表达这些cDNAs分子，可产生带有上述FcRII(CD32)单抗所定义的表位的免疫球蛋白结合分子。
The structural heterogeneity of the human low affinity receptor for IgG, FcRII(CD32), has been elucidated through the isolation, characterization, and expression of cDNA clones derived from myeloid and lymphoid RNA. These clones predict amino acid sequences consistent with integral membrane glycoproteins with single membrane spanning domains. The extracellular domains display sequence homology to other Fc gamma Rs and members of the Ig supergene family. A minimum of three genes (Fc gamma RIIa, IIa', and Fc gamma RIIb) encode these transcripts, which demonstrate highly related extracellular and membrane spanning domains. IIa/IIa' differ substantially in the intracytoplasmic domain from IIb. Alternative splicing of the IIb gene generates further heterogeneity in both NH2- and COOH-terminal domains of the predicted proteins. Comparison to the murine homologues of these molecules reveals a high degree of conservation between the products of one of these genes, Fc gamma RIIb, and the murine beta gene in primary sequence, splicing pattern, and tissue distribution. In contrast, the sequence of IIa' indicates its relationship to the beta-like genes, with mutation giving rise to a novel cytoplasmic domain, while IIa is a chimera of both alpha- and beta-like genes. Expression of these cDNA molecules by transfection results in the appearance of IgG binding molecules that bear the epitopes defined by the FcRII(CD32) mAbs previously described.