Genesis of the ILT/LIR/MIR clusters within the human leukocyte receptor complex
Genesis of the ILT/LIR/MIR clusters within the human leukocyte receptor complex
复制标题
人类白细胞受体复合体中 ILT/LIR/MIR 簇的起源
DOI：
10.1034/j.1600-065x.2001.1810103.x
复制
发表时间：
2001
影响因子：
8.7
通讯作者：
A. Ziegler
中科院分区：
文献类型：
--
作者：
A. Volz;H. Wende;K. Laun;A. Ziegler
摘要：人类白细胞受体复合体（LRC）包含至少26个属于免疫球蛋白超家族的基因。这些基因包括两个免疫球蛋白样转录物(ILT)/白细胞免疫球蛋白样受体(LIR)/单核-巨噬细胞抑制受体（MIR）基因簇，一个杀伤细胞抑制受体（KIR）基因簇，两个白细胞相关的免疫球蛋白样受体基因，以及IgA的Fc受体和天然细胞毒性受体1基因座。人们已经假设这些基因是通过多次复制进化而来的，而这两个ILT集群很可能是由一个古老的ILT集群的反向复制产生的。为了进一步阐明LRC中位点的可能起源，我们现在通过杂交研究了多种脊椎动物中KIR和ILT位点的存在，并比较了所有ILT基因的基因组序列。结果表明：1)KIR基因的起源可追溯到1亿年前，但只有灵长类动物与人类的KIR关系密切；2)相反，在鸟类中已经发现了可以用人类ILT cdna检测到的基因，这表明它们大约在3亿年前就存在了。利用人类基因组计划产生的序列数据，我们提出了一个假设，详细地重建了两个人类ILT集群的起源，这将有助于理解LRC的功能。
Summary: The human leukocyte receptor complex (LRC) contains at least 26 genes which belong to the immunoglobulin superfamily. The genes include two clusters of immunoglobulin‐like transcript (ILT)/leukocyte immunoglobulin‐like receptor (LIR)/monocyte‐macrophage inhibitory receptor (MIR) loci, a cluster of killer cell inhibitory receptor (KIR) genes, two leukocyte‐associated immunoglobulin‐like receptor genes, as well as the Fc receptor for IgA and the natural cytotoxicity receptor 1 loci. It has already been postulated that these genes have evolved by multiple duplications, while the two ILT clusters are likely to have been generated by the inverse duplication of an ancient ILT cluster. To shed more light on the possible origin of the loci within the LRC, we have now investigated the presence of KIR and ILT loci in a variety of vertebrates by hybridizations and compared the genomic sequences of all ILT genes. Our results lead to the following conclusions: 1) the origin of KIR genes dates back to about 100 million years, but only primate and human KIRs are closely related; 2) in contrast, genes which are detectable with human ILT cDNAs are already found in birds, suggesting their presence already about 300 million years ago. Using the sequence data produced by the human genome project, we have developed a hypothesis that reconstructs the genesis of the two human ILT clusters in detail which will help to understand the function of the LRC.