IMMUNOGENETICS OF NATURAL KILLER RECEPTORS

该项目的目的是利用免疫遗传学、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：1.人类杀伤免疫球蛋白（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物（LRC）的区域中。然而，在小鼠中，LRC不包含任何KIR基因。由于这个原因，人们认为小鼠缺乏KIR基因。与这种普遍持有的观点相反，我们在小鼠X染色体上发现了两个KIR样基因。2.我们发现小鼠没有伊加Fc受体基因（Fcar），而人类和大鼠的相应基因定位于LRC。沿着其他的观察结果，表明LRC的基因组结构在哺乳动物物种中有很大的不同。3.我们发现马有多个Ly49基因，但没有功能性KIR基因，表明Ly49在除啮齿动物以外的哺乳动物中也用作NK受体。该家族的V结构域显示出与T细胞和B细胞受体的实质性序列相似性。因此，该家族被命名为“类似于抗原受体的无配体配对受体（APAR）”，其可能作为NK受体发挥功能。

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)".