Natural killer cell receptors in the horse:: evidence for the existence of multiple transcribed LY49 genes

Natural killer cell receptors in the horse:: evidence for the existence of multiple transcribed LY49 genes
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DOI:
10.1002/eji.200324695
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发表时间:
2004-03-01
影响因子:
5.4
通讯作者:
Kasahara, M
Kasahara, M
中科院分区:
医学3区
文献类型:
--
作者:
Takahashi, T;Yawata, M;Kasahara, M

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在啮齿类动物中,Ly49家族编码与经典MHC I类分子相互作用的自然杀伤(NK)受体,而灵长类动物中的相应受体是杀伤细胞免疫球蛋白样受体(KIR)家族的成员。最近的证据表明,牛、家猫、狗和猪具有单一的LY49和多个KIR基因,这表明大多数非啮齿类哺乳动物中的主要NK受体可能是KIR。在这里,我们表明,马至少有六个LY49基因,五个免疫受体酪氨酸为基础的抑制基序(ITIM)和精氨酸在跨膜区。有趣的是,没有一个通过文库筛选分离的马KIR样cDNA克隆编码可能作为NK受体的分子;四种类型的克隆是KIR-Ig样转录本(KIR-ILT)杂交体,含有过早终止密码子和/或移码突变,两个推定的等位基因序列预测KIR3DL分子突变ITIM。据我们所知,这是第一个报告表明,非啮齿类哺乳动物可能使用LY49作为经典的MHC I类的NK受体。我们还表明,马脾表达ILT样基因与独特的结构域组织。辐射杂交定位和荧光原位杂交将马LY49和KIR/ILT基因分别定位于染色体6q13和10p12。
In rodents, the Ly49 family encodes natural killer (NK) receptors interacting with classical MHC class I molecules, whereas the corresponding receptors in primates are members of the killer cell immunoglobulin-like receptor (KIR) family. Recent evidence indicates that the cattle, domestic cat, dog, and pig have a single LY49 and multiple KIR genes, suggesting that predominant NK receptors in most non-rodent mammals might be KIR. Here, we show that the horse has at least six LY49 genes, five with an immunoreceptor tyrosine-based inhibition motif (ITIM) and one with arginine in the transmembrane region. Interestingly, none of the horse KIR-like cDNA clones isolated by library screening encoded molecules likely to function as NK receptors; four types of clones were KIR-Ig-like transcript (KIR-ILT) hybrids and contained premature stop codons and/or frameshift mutations, and two putative allelic sequences predicting KIR3DL molecules had mutated ITIM. To our knowledge, this is the first report suggesting that non-rodent mammals may use LY49 as NK receptors for classical MHC class I. We also show that horse spleen expresses ILT-like genes with unique domain organizations. Radiation hybrid mapping and fluorescence in situ hybridization localized horse LY49 and KIR/ILT genes to chromosomes 6q13 and 10p12, respectively.