Karolinska Institutet, Stockholm, Sweden.
Blood. 2013 Jun 6;121(23):4703-7. doi: 10.1182/blood-2012-10-461442. Epub 2013 May 1.
Natural killer (NK) cells are functionally tuned by education via killer cell immunoglobulin receptors (KIRs) interacting with HLA class I molecules. We examined the effect of KIR gene copy number variation on the education of human NK cells. The frequency of NK cells expressing a given KIR correlated with the copy number of that gene. However, coexpression of multiple copies from a single locus, or duplicated loci, was infrequent, which is in line with independent transcriptional regulation of each allele or copy. Intriguingly, coexpression of 2 KIR alleles, resulting in higher surface expression, did not lead to enhanced functional responses in vitro or to selective advantages during in vivo responses to cytomegalovirus infection, suggesting that receptor density does not influence NK education at the single cell level. However, individuals with multiple KIR gene copies had higher frequencies of responding cells, consistent with heightened overall responsiveness.
自然杀伤 (NK) 细胞通过杀手细胞免疫球蛋白受体 (KIR) 与 HLA Ⅰ类分子相互作用而受到功能调节。我们研究了 KIR 基因拷贝数变异对人类 NK 细胞教育的影响。表达给定 KIR 的 NK 细胞的频率与该基因的拷贝数相关。然而，来自单个基因座或重复基因座的多个拷贝的共表达很少见，这与每个等位基因或拷贝的独立转录调控一致。有趣的是，2 个 KIR 等位基因的共表达导致表面表达增加，但不会导致体外功能反应增强，或在体内对巨细胞病毒感染的反应中具有选择性优势，这表明受体密度不会影响 NK 细胞在单细胞水平的教育。然而，具有多个 KIR 基因拷贝的个体具有更高频率的反应细胞，这与更高的整体反应性一致。
