Matched Sizes of Activating and Inhibitory Receptor/Ligand Pairs Are Required for Optimal Signal Integration by Human Natural Killer Cells
Copyright policy )Matched Sizes of Activating and Inhibitory Receptor/Ligand Pairs Are Required for Optimal Signal Integration by Human Natural Killer Cells
It has been suggested that receptor-ligand complexes segregate or co-localise within immune synapses according to their size, and this is important for receptor signaling. Here, we set out to test the importance of receptor-ligand complex dimensions for immune surveillance of target cells by human Natural Killer (NK) cells. NK cell activation is regulated by integrating signals from activating receptors, such as NKG2D, and inhibitory receptors, such as KIR2DL1. Elongating the NKG2D ligand MICA reduced its ability to trigger NK cell activation. Conversely, elongation of KIR2DL1 ligand HLA-C reduced its ability to inhibit NK cells. Whereas normal-sized HLA-C was most effective at inhibiting activation by normal-length MICA, only elongated HLA-C could inhibit activation by elongated MICA. Moreover, HLA-C and MICA that were matched in size co-localised, whereas HLA-C and MICA that were different in size were segregated. These results demonstrate that receptor-ligand dimensions are important in NK cell recognition, and suggest that optimal integration of activating and inhibitory receptor signals requires the receptor-ligand complexes to have similar dimensions.
- University of Oxford United Kingdom
- National University of Singapore Singapore
- University of Warwick United Kingdom
- University of Salford United Kingdom
- Imperial College London United Kingdom
HLA-C, IMMUNOLOGICAL SYNAPSE, HLA antigen class 1, animal cell, protein binding, ligand, confocal microscopy, Ligands, Lymphocyte Activation, Receptors, Killer Cells, killer cell immunoglobulin like receptor 2DL1, genetics, CRYSTAL-STRUCTURE, IMMUNE SYNAPSES, Microscopy, Microscopy, Confocal, KIR2DL1 protein, MHC class I-related chain A, KLRK1 protein, Q, article, immunological synapse, R, cell line, HLA C antigen, protein mica, unclassified drug, cell activation, natural killer cell lectin like receptor subfamily K, Multidisciplinary Sciences, Killer Cells, Natural, NK Cell Lectin-Like Receptor Subfamily K, Confocal, B-CELLS, Receptors, KIR2DL1, Natural, Science & Technology - Other Topics, Medicine, NK CELLS, signal transduction, Research Article, Protein Binding, Signal Transduction, 570, General Science & Technology, Science, Recombinant Fusion Proteins, Molecular Sequence Data, 610, protein localization, HLA-C Antigens, Cell Line, MHC class I related chain A, complex formation, MD Multidisciplinary, Humans, controlled study, human, Amino Acid Sequence, cell contact, mouse, photoprotein, lymphocyte activation, hybrid protein, nonhuman, Science & Technology, RNA translation, human cell, Histocompatibility Antigens Class I, natural killer cell, QP, amino acid sequence, KIR2DL1, MHC CLASS-I, carrier protein, Luminescent Proteins, natural killer cell receptor NKG2D, molecular genetics, T-CELLS, TARGET-CELLS, LIGAND, metabolism
HLA-C, IMMUNOLOGICAL SYNAPSE, HLA antigen class 1, animal cell, protein binding, ligand, confocal microscopy, Ligands, Lymphocyte Activation, Receptors, Killer Cells, killer cell immunoglobulin like receptor 2DL1, genetics, CRYSTAL-STRUCTURE, IMMUNE SYNAPSES, Microscopy, Microscopy, Confocal, KIR2DL1 protein, MHC class I-related chain A, KLRK1 protein, Q, article, immunological synapse, R, cell line, HLA C antigen, protein mica, unclassified drug, cell activation, natural killer cell lectin like receptor subfamily K, Multidisciplinary Sciences, Killer Cells, Natural, NK Cell Lectin-Like Receptor Subfamily K, Confocal, B-CELLS, Receptors, KIR2DL1, Natural, Science & Technology - Other Topics, Medicine, NK CELLS, signal transduction, Research Article, Protein Binding, Signal Transduction, 570, General Science & Technology, Science, Recombinant Fusion Proteins, Molecular Sequence Data, 610, protein localization, HLA-C Antigens, Cell Line, MHC class I related chain A, complex formation, MD Multidisciplinary, Humans, controlled study, human, Amino Acid Sequence, cell contact, mouse, photoprotein, lymphocyte activation, hybrid protein, nonhuman, Science & Technology, RNA translation, human cell, Histocompatibility Antigens Class I, natural killer cell, QP, amino acid sequence, KIR2DL1, MHC CLASS-I, carrier protein, Luminescent Proteins, natural killer cell receptor NKG2D, molecular genetics, T-CELLS, TARGET-CELLS, LIGAND, metabolism
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