Takahashi Tomoko, Yawata Makoto, Raudsepp Terje, Lear Teri L, Chowdhary Bhanu P, Antczak Douglas F, Kasahara Masanori
Department of Biosystems Science, School of Advanced Sciences, The Graduate University for Advanced Studies (Sokendai), Hayama, Japan.
present address: Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305-5126, USA.
Eur J Immunol. 2004 Mar;34(3):773-784. doi: 10.1002/eji.200324695.
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 asNK 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.
在啮齿动物中，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、狗和猪有一个单一的LY49基因和多个KIR基因，这表明大多数非啮齿动物哺乳动物中的主要NK受体可能是KIR。在这里，我们表明马至少有六个LY49基因，其中五个带有基于免疫受体酪氨酸的抑制基序（ITIM），一个在跨膜区域带有精氨酸。有趣的是，通过文库筛选分离出的马KIR样cDNA克隆中，没有一个编码可能作为NK受体发挥作用的分子；四种类型的克隆是KIR-Ig样转录本（KIR-ILT）杂种，包含提前终止密码子和/或移码突变，预测为KIR3DL分子的两个推定等位基因序列具有突变的ITIM。据我们所知，这是第一份表明非啮齿动物哺乳动物可能使用LY49作为经典MHC I类的NK受体的报告。我们还表明马脾脏表达具有独特结构域组织的ILT样基因。辐射杂种图谱和荧光原位杂交分别将马LY49和KIR/ILT基因定位到6号染色体的q13和10号染色体的p12。
