Abstract:
:KIR2DL5 (CD158f) is the most recently identified inhibitory member of human killer-cell Ig-like receptors (KIRs), which enable NK cells to sense self-HLA. Unlike KIR2DL1-3, recognizing HLA-C allotypes through Ig-like domains of the D1-D2 type, KIR2DL5 shares a D0-D2 configuration with KIR2DL4, and its ligands have not been identified. KIR2DL5 is encoded by two paralogous genes displaying copy number variation and allelic polymorphism-KIR2DL5A and KIR2DL5B. UP-R1 mAb, raised against the common allele KIR2DL5A*001, enables specific KIR2DL5 detection. However, not every KIR2DL5+ individual has NK cells staining with UP-R1, discrepancy explained in part by epigenetically silent KIR2DL5B alleles with a distinctive substitution in a promoter RUNX-binding site. Furthermore, we show here that the transcribed allele KIR2DL5A*005, second most common of its locus, fails to confer NK cells UP-R1 reactivity, phenotype explained by inefficacious transport of its product to the cell surface. Two amino acid substitutions distinguish the KIR2DL5A*005 and *001 coding regions. Western blot, flow cytometry, and confocal microscopy analyses of cells transfected with tagged constructs demonstrate that a serine substitution for glycine-174, conserved in most KIR, is mainly responsible for KIR2DL5A*005 intracellular retention, and it also affects mAb recognition. In contrast, substitution of aspartate for asparagine 152 has only a minor effect on surface expression, despite destroying an otherwise conserved N-glycosylation site. Our results help to explain the variable expression profile of KIR2DL5+ subjects and indicate that functional polymorphisms in both its promoter and its coding regions are critical for understanding the KIR2DL5 role in immunity and its importance for human health.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Cisneros E,Estefanía E,Vilches Cdoi
10.3389/fimmu.2016.00698subject
Has Abstractpub_date
2017-01-17 00:00:00pages
698issn
1664-3224journal_volume
7pub_type
杂志文章abstract::Induction of immune tolerance is a key process by which the immune system is educated to modulate reactions against benign stimuli such as self-antigens and commensal microbes. Understanding and harnessing the natural mechanisms of immune tolerance may become an increasingly useful strategy for treating many types of ...
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pub_type: 杂志文章,评审
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pub_type: 杂志文章,评审
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
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pub_type: 杂志文章,评审
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journal_title:Frontiers in immunology
pub_type: 杂志文章,meta分析
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journal_title:Frontiers in immunology
pub_type: 杂志文章
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更新日期:2013-08-26 00:00:00
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pub_type: 杂志文章,评审
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journal_title:Frontiers in immunology
pub_type:
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2014.00096
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pub_type: 杂志文章
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journal_title:Frontiers in immunology
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pub_type: 杂志文章,评审
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journal_title:Frontiers in immunology
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
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journal_title:Frontiers in immunology
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pub_type: 杂志文章,评审
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pub_type: 杂志文章
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