ArticlePLoS genetics2018
Identification of an elaborate NK-specific system regulating HLA-C expression.
Article in PLoS genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- Article
- HLA-C expression in extravillous trophoblasts is determined by an ELF3-NLRP2/NLRP7 regulatory axis.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- The role of extravillous trophoblasts and uterine NK cells in vascular remodeling during pregnancy.Frontiers in immunology · 2022Review
- The New Kid on the Block: HLA-C, a Key Regulator of Natural Killer Cells in Viral Immunity.Cells · 2021Review
- Relevance of Polymorphic KIR and HLA Class I Genes in NK-Cell-Based Immunotherapies for Adult Leukemic Patients.Cancers · 2021Review
- Exome Sequencing Reveals a Putative Role for HLA-C*03:02 in Control of HIV-1 in African Pediatric Populations.Frontiers in genetics · 2021Article
- Three types of HLA-G+ extravillous trophoblasts that have distinct immune regulatory properties.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Tuning of human NK cells by endogenous HLA-C expression.Immunogenetics · 2020Review
- Single Nucleotide Polymorphism inFrontiers in immunology · 2020Article
- Genetics of antigen processing and presentation.Immunogenetics · 2019Review
- On the Way to Become a Natural Killer Cell.Frontiers in immunology · 2019Review
- Tuning of NK-Specific HLA-C Expression by Alternative mRNA Splicing.Frontiers in immunology · 2019Article
- HLA-B and HLA-C Differ in Their Nanoscale Organization at Cell Surfaces.Frontiers in immunology · 2019Article
- The MHC in the era of next-generation sequencing: Implications for bridging structure with function.Human immunology · 2019Review
- Novel Approach to Cell Surface Discrimination Between KIR2DL1 Subtypes and KIR2DS1 Identifies Hierarchies in NK Repertoire, Education, and Tolerance.Frontiers in immunology · 2019Article
- The Dual Role of HLA-C in Tolerance and Immunity at the Maternal-Fetal Interface.Frontiers in immunology · 2019Review
- Article
- Review
- Generalists and Specialists: A New View of How MHC Class I Molecules Fight Infectious Pathogens.Trends in immunology · 2018Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
The HLA-C gene appears to have evolved in higher primates to serve as a dominant source of ligands for the KIR2D family of inhibitory MHC class I receptors. The expression of NK cell-intrinsic MHC class I has been shown to regulate the murine Ly49 family of MHC class I receptors due to the interaction of these receptors with NK cell MHC in cis. However, cis interactions have not been demonstrated for the human KIR and HLA proteins. We report the discovery of an elaborate NK cell-specific system regulating HLA-C expression, indicating an important role for HLA-C in the development and function of NK cells. A large array of alternative transcripts with differences in intron/exon content are generated from an upstream NK-specific HLA-C promoter, and exon content varies between HLA-C alleles due to SNPs in splice donor/acceptor sites. Skipping of the first coding exon of HLA-C generates a subset of untranslatable mRNAs, and the proportion of untranslatable HLA-C mRNA decreases as NK cells mature, correlating with increased protein expression by mature NK cells. Polymorphism in a key Ets-binding site of the NK promoter has generated HLA-C alleles that lack significant promoter activity, resulting in reduced HLA-C expression and increased functional activity. The NK-intrinsic regulation of HLA-C thus represents a novel mechanism controlling the lytic activity of NK cells during development.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.