Natural LILRB1 D1-D2 variants show frequency differences in populations and bind to HLA class I with various avidities.
Natural LILRB1 D1-D2 variants show frequency differences in populations and bind to HLA class I with various avidities.
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DOI：
10.1007/s00251-022-01264-7
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发表时间：
2022-12
期刊：
影响因子：
3.2
通讯作者：
Guethlein, Lisbeth A.
中科院分区：
文献类型：
--
作者：
Liu, Fuguo;Cocker, Alexander T. H.;Pugh, Jason L.;Djaoud, Zakia;Parham, Peter;Guethlein, Lisbeth A.
白细胞免疫球蛋白样受体B1（LILRB 1）广泛表达于各种免疫细胞上，LILRB 1与HLA I类和病原体衍生蛋白的接合可以调节免疫应答。在本研究中，通过从1000个基因组第3阶段数据库中筛选LILRB 1基因座鉴定了108个LILRB 1等位基因。在3个或更多个体中出现的46个等位基因编码28种LILRB 1同种异型，然后将推断的LILRB 1同种异型分组为9种LILRB 1 D1-D2变体以供进一步分析。我们发现变体1、2和3代表了三种最常见的LILRB 1 D1-D2变体，并且九种变体在人群中显示出频率差异。结合测定证明变体1以最高亲合力结合HLA I类，并且所有测试的LILRB 1 D1-D2变体以比结合HLA-A和-B低的亲合力结合HLA-C。在HLA I类中的位置183、189和268处的基因座特异性多态性以及HLA-A（位置207和253）和HLA-B（位置194）中的二态性影响它们与LILRB 1的结合。值得注意的是，静电相互作用在LILRB 1与HLA I类的结合中起着关键作用，如通过静电分析和通过比较LILRB 1的位置72和103处的多态性引起的不同结合亲合力所揭示的。在本文中，我们提出了一个全面的研究群体遗传学和LILRB 1的结合能力。这些数据将有助于我们更好地了解LILRB 1相关的免疫系统多样性，并为功能研究奠定基础。在线版本包含补充材料，可通过10.1007/s 00251 -022-01264-7获得。
Leukocyte immunoglobulin-like receptor B1 (LILRB1) is widely expressed on various immune cells and the engagement of LILRB1 to HLA class I and pathogen-derived proteins can modulate the immune response. In the current study, 108 LILRB1 alleles were identified by screening the LILRB1 locus from the 1000 Genomes Phase 3 database. Forty-six alleles that occurred in three or more individuals encode 28 LILRB1 allotypes, and the inferred LILRB1 allotypes were then grouped into 9 LILRB1 D1-D2 variants for further analysis. We found that variants 1, 2, and 3 represent the three most frequent LILRB1 D1-D2 variants and the nine variants show frequency differences in populations. The binding assay demonstrated that variant 1 bound to HLA class I with the highest avidity, and all tested LILRB1 D1-D2 variants bound to HLA-C with lower avidity than to HLA-A and -B. Locus-specific polymorphisms at positions 183, 189, and 268 in HLA class I and dimorphisms in HLA-A (positions 207 and 253) and in HLA-B (position 194) affect their binding to LILRB1. Notably, the electrostatic interaction plays a critical role in the binding of LILRB1 to HLA class I as revealed by electrostatic analysis and by comparison of different binding avidities caused by polymorphisms at positions 72 and 103 of LILRB1. In this paper, we present a comprehensive study of the population genetics and binding abilities of LILRB1. The data will help us better understand the LILRB1-related diversity of the immune system and lay a foundation for functional studies. The online version contains supplementary material available at 10.1007/s00251-022-01264-7.
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