鉴定有袋动物袋獾(Sarcophilus harrisii)基因组中的自然杀伤细胞受体基因。

Identification of natural killer cell receptor genes in the genome of the marsupial Tasmanian devil (Sarcophilus harrisii).

机构信息

Faculty of Veterinary Science, University of Sydney, B19 RMC Gunn, Sydney, NSW 2006, Australia.

出版信息

Immunogenetics. 2013 Jan;65(1):25-35. doi: 10.1007/s00251-012-0643-z. Epub 2012 Sep 25.

Abstract

Within the mammalian immune system, natural killer (NK) cells contribute to the first line of defence against infectious agents and tumours. Their activity is regulated, in part, by cell surface NK cell receptors. NK receptors can be divided into two unrelated, but functionally analogous superfamilies based on the structure of their extracellular ligand-binding domains. Receptors belonging to the C-type lectin superfamily are predominantly encoded in the natural killer complex (NKC), while receptors belonging to the immunoglobulin superfamily are predominantly encoded in the leukocyte receptor complex (LRC). Natural killer cell receptors are emerging as a rapidly evolving gene family which can display significant intra- and interspecific variation. To date, most studies have focused on eutherian mammals, with significantly less known about the evolution of these receptors in marsupials. Here, we describe the identification of 43 immunoglobulin domain-containing LRC genes in the genome of the Tasmanian devil (Sarcophilus harrisii), the largest remaining marsupial carnivore and only the second marsupial species to be studied. We also identify orthologs of NKC genes KLRK1, CD69, CLEC4E, CLEC1B, CLEC1A and an ortholog of an opossum NKC receptor. Characterisation of these regions in a second, distantly related marsupial provides new insights into the dynamic evolutionary histories of these receptors in mammals. Understanding the functional role of these genes is also important for the development of therapeutic agents against Devil Facial Tumour Disease, a contagious cancer that threatens the Tasmanian devil with extinction.

摘要

在哺乳动物的免疫系统中,自然杀伤 (NK) 细胞有助于抵御传染病原体和肿瘤的第一道防线。它们的活性受到细胞表面 NK 细胞受体的部分调节。根据其细胞外配体结合域的结构,NK 受体可分为两个不相关但功能类似的超家族。属于 C 型凝集素超家族的受体主要编码在自然杀伤细胞复合物 (NKC) 中,而属于免疫球蛋白超家族的受体主要编码在白细胞受体复合物 (LRC) 中。NK 细胞受体作为一个快速进化的基因家族正在出现,其在种内和种间都可以显示出显著的变异性。迄今为止,大多数研究都集中在真兽类哺乳动物上,对这些受体在有袋类动物中的进化了解甚少。在这里,我们描述了在塔斯马尼亚恶魔(Sarcophilus harrisii)基因组中鉴定出的 43 个含有免疫球蛋白结构域的 LRC 基因,塔斯马尼亚恶魔是现存最大的有袋类食肉动物,也是第二个被研究的有袋类动物物种。我们还鉴定了 NKC 基因 KLRK1、CD69、CLEC4E、CLEC1B、CLEC1A 和负鼠 NKC 受体的同源基因。在第二个亲缘关系较远的有袋动物中对这些区域进行的特征描述为这些受体在哺乳动物中的动态进化历史提供了新的见解。了解这些基因的功能作用对于开发针对恶魔面部肿瘤病(一种威胁塔斯马尼亚恶魔灭绝的传染性癌症)的治疗剂也很重要。

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