Genetic control of natural killing and in vivo tumor elimination by the Chok locus
Genetic control of natural killing and in vivo tumor elimination by the Chok locus
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DOI：
10.1084/jem.188.12.2243
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发表时间：
1998-12-21
影响因子：
15.3
通讯作者：
Yokoyama, WM
中科院分区：
文献类型：
--
作者：
Idris, AH;Iizuka, K;Yokoyama, WM
在自然杀伤过程中，靶点识别的分子机制还不清楚。剖析自然杀伤（NK）细胞识别的复杂性的一种方法是通过利用近交系小鼠品系之间的遗传差异。在这项研究中，我们确定白细胞介素2激活的BALB/c衍生的NK细胞不能像C57 BL/6衍生的NK细胞那样有效地裂解中国仓鼠卵巢（CHO）细胞，尽管其杀死其他靶点的能力相当。这种菌株确定的差异也表现出新鲜分离的NK细胞，并确定为独立的主机主要组织相容性单倍型。此外，CHO杀伤与NK1.1或2B 4活化分子的表达无关。遗传作图研究揭示了影响CHO杀伤的基因座（称为Chok）与NK基因复合物（NKC）内编码的基因座之间的连锁，表明Chok编码CHO细胞特异性NK细胞受体。体内试验概括了体外数据，两项研究均确定Chok调节NK穿孔素依赖性细胞毒性过程。这些结果可能对NK细胞在异种移植排斥反应中的作用有影响。我们的遗传分析表明Chok是一个影响NK细胞介导的细胞毒性的单一基因座，类似于其他也调节NK细胞复杂活性的NKC基因座。
The molecular mechanisms underlying target recognition during natural killing are not well understood. One approach to dissect the complexities of natural killer (NK) cell recognition is through exploitation of genetic differences among inbred mouse strains. In this study, we determined that interleukin 2-activatd BALB/c-derived NK cells could not lyse Chinese hamster ovary (CHO) cells as efficiently as C57BL/6-derived NK cells, despite equivalent capacity to kill other targets. This strain-determined difference was also exhibited by freshly isolated NK cells, and was determined to be independent of host major histocompatibility haplotype. Furthermore, CHO killing did not correlate with expression of NK1.1 or 2B4 activation molecules. Genetic mapping studies revealed linkage between the locus influencing CHO kiling, termed Chok, and loci encoded within the NK gene complex (NKC), suggesting that Chok encodes an NK cell receptor specific for CHO cells. In vivo assays recapitulated the in vitro data, and both studies determined that Chok regulates an NK perforin-dependent cytotoxic process. These results may have implications for the role of NK cells in xenograft rejection. Our genetic analysis suggests Chok is a single locus that affects NK cell-mediated cytotoxicity similar to other NKC loci that also regulate the complex activity of NK cells.