Wang L L, Mehta I K, LeBlanc P A, Yokoyama W M
Department of Medicine and Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA.
J Immunol. 1997 Jan 1;158(1):13-7.
NK cells express MHC class I-specific receptors that inhibit tumor killing. In mice, these receptors belong to the highly polymorphic Ly-49 family, which are type II integral membrane proteins homologous to C-type lectins. In contrast, human killer inhibitory receptors (KIR) are type I transmembrane proteins that display minimal allelism and belong to the Ig superfamily. These structural differences suggested that each species evolved distinct receptors to subserve the same function. In this report, however, we show that mouse NK and LAK cells and NK cell clones express full-length transcripts for gp49B1, an immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing type I transmembrane protein belonging to the Ig superfamily, and displaying minimal allelism by Southern and sequence analysis. By flow cytometry, gp49B1 is expressed on all NK cells. Therefore, we have established that gp49B1, a structural homologue of human KIR, is expressed on mouse NK cells. This strongly suggests that NK cells express two structurally distinct types of inhibitory receptors and that these receptors may act as coreceptors in mediating inhibition.
自然杀伤(NK)细胞表达抑制肿瘤杀伤的MHC I类特异性受体。在小鼠中,这些受体属于高度多态的Ly-49家族,它们是与C型凝集素同源的II型整合膜蛋白。相比之下,人类杀伤抑制受体(KIR)是I型跨膜蛋白,其等位基因多态性极低,属于免疫球蛋白超家族。这些结构差异表明,每个物种都进化出了不同的受体来行使相同的功能。然而,在本报告中,我们发现小鼠NK细胞、淋巴因子激活的杀伤(LAK)细胞以及NK细胞克隆表达gp49B1的全长转录本,gp49B1是一种含有基于免疫受体酪氨酸的抑制基序(ITIM)的I型跨膜蛋白,属于免疫球蛋白超家族,通过Southern杂交和序列分析显示其等位基因多态性极低。通过流式细胞术检测,gp49B1在所有NK细胞上均有表达。因此,我们确定gp49B1作为人类KIR的结构同源物,在小鼠NK细胞上表达。这有力地表明,NK细胞表达两种结构不同的抑制性受体,并且这些受体可能作为共受体参与介导抑制作用。