Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
Hum Immunol. 2010 Oct;71(10):942-9. doi: 10.1016/j.humimm.2010.06.015. Epub 2010 Jun 30.
Leukocyte Ig-like receptor (LIR)-1 is an inhibitory receptor that binds a broad range of class I HLA molecules and is encoded by the LILRB1 gene within the leukocyte receptor complex. In contrast to uniform expression on monocytes and B cells, LIR-1 expression on natural killer (NK) cells varies considerably between individuals. To investigate how polymorphism is related to the observed patterns of expression, we analyzed the LILRB1 gene and its transcriptional activity in a group of individuals with various levels of expression on NK cells. We found that LILRB1 transcription is correlated with surface protein expression on NK cells. In a cohort of 24 donors, we found high expression on NK cells to be associated with three linked SNPs (AGG verses GAA) within the putative regulatory region. We also identified several new protein variants and observed variants with P, T, T, and I at positions 68, 95, 142, and 155, respectively, more frequently in donors with low expression on NK cells. These results suggest that there is a significant degree of diversity within the LILRB1 locus and that it influences expression patterns on NK cells. These genetic differences may underpin variation in individual immune responses involving LIR-1 on NK cells.
白细胞免疫球蛋白样受体 (LIR)-1 是一种抑制性受体，它可以结合广泛的 I 类 HLA 分子，由白细胞受体复合物中的 LILRB1 基因编码。与单核细胞和 B 细胞上的均匀表达不同，自然杀伤 (NK) 细胞上的 LIR-1 表达在个体之间差异很大。为了研究多态性与观察到的表达模式之间的关系，我们在一群 NK 细胞表达水平不同的个体中分析了 LILRB1 基因及其转录活性。我们发现 LILRB1 转录与 NK 细胞表面蛋白表达相关。在 24 名供体的队列中，我们发现 NK 细胞上的高表达与假定调节区域内的三个连锁 SNP（AGG 对 GAA）相关。我们还鉴定了几种新的蛋白质变体，并观察到在 NK 细胞表达较低的供体中，分别在位置 68、95、142 和 155 处具有 P、T、T 和 I 的变体更频繁。这些结果表明，LILRB1 基因座内存在显著程度的多样性，并且影响 NK 细胞上的表达模式。这些遗传差异可能是涉及 NK 细胞上 LIR-1 的个体免疫反应变化的基础。
