LILRB1 polymorphism and surface phenotypes of natural killer cells
LILRB1 polymorphism and surface phenotypes of natural killer cells
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DOI：
10.1016/j.humimm.2010.06.015
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发表时间：
2010-10-01
期刊：
影响因子：
2.7
通讯作者：
Burshtyn, Deborah N.
中科院分区：
文献类型：
--
作者：
Davidson, Chelsea L.;Li, Nicholas L.;Burshtyn, Deborah N.
白细胞免疫球蛋白样受体(LIR)-1是一种抑制性受体，与广泛的人类白细胞抗原I类分子结合，由白细胞受体复合体中的LILRB1基因编码。与单核细胞和B细胞的统一表达不同，自然杀伤(NK)细胞上LIR-1的表达在个体之间有很大的差异。为了研究多态与观察到的表达模式之间的关系，我们分析了一组在NK细胞上有不同水平表达的个体的LILRB1基因及其转录活性。我们发现LILRB1的转录与NK细胞表面蛋白的表达有关。在24名捐献者的队列中，我们发现NK细胞上的高表达与推测调控区域内的三个连锁SNP(AGG与GM)相关。我们还发现了几个新的蛋白质变异，并观察到在68、95、142和155位分别有P、T、T和1的变异，在NK细胞低表达的捐赠者中更常见。这些结果表明，LILRB1基因座存在显著程度的多样性，并影响NK细胞的表达模式。这些遗传差异可能是NK细胞上涉及LIR-1的个体免疫反应差异的基础。(C)2010年美国组织相容性和免疫遗传学学会。爱思唯尔公司出版，版权所有。
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 GM) within the putative regulatory region. We also identified several new protein variants and observed variants with P, T, T, and 1 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. (C) 2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.