ArticleScience signaling2019
Genetic diversity affects the nanoscale membrane organization and signaling of natural killer cell receptors.
Article in Science signaling, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- Resting-state spatial statistics of NK cell receptors may improve early signal discrimination.Biophysical journal · 2026Article
- Nanoscale restructuring of the immune synapse with an engager enhances NK cell function.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- RBM47 promotes cell proliferation and immune evasion by upregulating PDIA6: a novel mechanism of pancreatic cancer progression.Journal of translational medicine · 2024Article
- Ligand-induced segregation from large cell-surface phosphatases is a critical step in γδ TCR triggering.Cell reports · 2024Article
- Spatial localization of CD16a at the human NK cell ADCC lytic synapse.bioRxiv : the preprint server for biology · 2024Article
- TIGIT can inhibit T cell activation via ligation-induced nanoclusters, independent of CD226 co-stimulation.Nature communications · 2023Article
- Ablation of SYK Kinase from Expanded Primary Human NK Cells via CRISPR/Cas9 Enhances Cytotoxicity and Cytokine Production.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Circulating natural killer cells and their association with breast cancer and its clinico-pathological characteristics.Ecancermedicalscience · 2023Article
- Measuring the Co-Localization and Dynamics of Mobile Proteins in Live Cells Undergoing Signaling Responses.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Evaluation of telomeric KIR genes and their association with CMV infection in kidney transplant recipients.Immunogenetics · 2022Article
- Licensing Natural Killers for Antiviral Immunity.Pathogens (Basel, Switzerland) · 2021Review
- Low number of KIR ligands in lymphoma patients favors a good rituximab-dependent NK cell response.Oncoimmunology · 2021Article
- Efficient Cross-Correlation Filtering of One- and Two-Color Single Molecule Localization Microscopy Data.Frontiers in bioinformatics · 2021Review
- The Role of the Cytoskeleton in Regulating the Natural Killer Cell Immune Response in Health and Disease: From Signaling Dynamics to Function.Frontiers in cell and developmental biology · 2021Review
- Killer Cell Immunoglobulin-like Receptor Variants Are Associated with Protection from Symptoms Associated with More Severe Course in Parkinson Disease.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Genetic diversity in human natural killer (NK) cell receptors is linked to resistance and susceptibility to many diseases. Here, we tested the effect of this diversity on the nanoscale organization of killer cell immunoglobulin-like receptors (KIRs). Using superresolution microscopy, we found that inhibitory KIRs encoded by different genes and alleles were organized differently at the surface of primary human NK cells. KIRs that were found at low abundance assembled into smaller clusters than those formed by KIRs that were more highly abundant, and at low abundance, there was a greater proportion of KIRs in clusters. Upon receptor triggering, a structured interface called the immune synapse assembles, which facilitates signal integration and controls NK cell responses. Here, triggering of low-abundance receptors resulted in less phosphorylation of the downstream phosphatase SHP-1 but more phosphorylation of the adaptor protein Crk than did triggering of high-abundance receptors. In cells with greater KIR abundance, SHP-1 dephosphorylated Crk, which potentiated NK cell spreading during activation. Thus, genetic variation modulates both the abundance and nanoscale organization of inhibitory KIRs. That is, as well as the number of receptors at the cell surface varying with genotype, the way in which these receptors are organized in the membrane also varies. Essentially, a change in the average surface abundance of a protein at the cell surface is a coarse descriptor entwined with changes in local nanoscale clustering. Together, our data indicate that genetic diversity in inhibitory KIRs affects membrane-proximal signaling and, unexpectedly, the formation of activating immune synapses.
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