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IMMUNOGENETICS OF NATURAL KILLER RECEPTORS

自然杀伤受体的免疫遗传学

基本信息

批准号：
14370111
负责人：
KASAHARA Masanori
金额：
$ 7.49万
依托单位：
HOKKAIDO UNIVERSITY (2004)The Graduate University for Advanced Studies (2002-2003)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370111/
关键词：
Natural killer receptors KIR IgA Fc receptors Ly49 Leukocyte receptor complex IgA Fc レセプター LY49 ウマ leukocyte receptor complex NKレセプター MILL分子

项目摘要

The aims of this project were to study the structure, function and evolution of natural killer (NK) receptors and their ligands using multidisciplinary approaches such as immunogenetics, comparative genomics and immunobiology. Major research accomplishments were as follows :1.In humans, killer immunoglobulin (Ig)-like receptors (KIR) function as major NK receptors for HLA class I molecules. The genes coding for KIR are located in the region known as the leukocyte receptor complex (LRC). In mice, however, the LRC does not contain any KIR genes. For this reason, it has been assumed that mice lack KIR genes. Contrary to this widely-held belief, we identified two KIR-like genes on mouse chromosome X. These genes were named Kirl (KIR-like).2.We found that mice do not have the IgA Fc receptor gene (Fcar), the human and rat counterparts of which map to the LRC. This observation, along with others, indicated that the genomic organization of the LRC differs substantially among mammalian species.3.We have found that the horse has multiple Ly49 genes but no functional KIR genes, indicating that Ly49 are also used as NK receptors in mammals other than rodents.4.We have identified a family of hagfish genes with features characteristic of paired Ig-like receptors. The V domain of this family shows substantial sequence similarity to that of T-cell and B-cell receptors. Hence, this family, which may function as NK receptors, was named "agnathan paired receptors resembling antigen receptors (APAR)".

本项目旨在利用免疫遗传学、比较基因组学和免疫生物学等多学科方法研究自然杀伤（NK）受体及其配体的结构、功能和进化。主要研究成果如下：在人类中，杀伤免疫球蛋白（Ig）样受体（KIR）是HLA I类分子的主要NK受体。编码KIR的基因位于称为白细胞受体复合体（LRC）的区域。然而，在小鼠中，LRC不含任何KIR基因。因此，人们一直认为老鼠缺乏KIR基因。与人们普遍持有的观点相反，我们在小鼠x染色体上发现了两个类似Kirl的基因，这些基因被命名为Kirl （Kirl -like）。我们发现小鼠没有IgA Fc受体基因（Fcar），而人类和大鼠的对应基因则指向LRC。这一观察结果以及其他一些观察结果表明，哺乳动物物种之间LRC的基因组组织存在很大差异。我们发现马有多个Ly49基因，但没有功能性的KIR基因，这表明Ly49在啮齿类动物以外的哺乳动物中也被用作NK受体。我们已经确定了一个盲鳗家族的基因与配对igg样受体的特征。该家族的V结构域与t细胞和b细胞受体的序列具有很大的相似性。因此，这个可能具有NK受体功能的家族被命名为“类似抗原受体的agnathan配对受体（APAR）”。