1. Matched Sizes of Activating and Inhibitory Receptor/Ligand Pairs Are Required for Optimal Signal Integration by Human Natural Killer Cells
- Author
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Stephane Oddos, Philipp Eissmann, Alice Harrison, Keith G. Gould, Joanna Brzostek, Shaun-Paul Cordoba, Shiqiu Xiong, Karsten Köhler, Maryam Mehrabi, Nigel J. Burroughs, Vladimir Miloserdov, Daniel M. Davis, Philip Anton van der Merwe, and Medical Research Council (MRC)
- Subjects
HLA-C ,IMMUNOLOGICAL SYNAPSE ,Cell ,lcsh:Medicine ,Antigen Processing and Recognition ,NK cells ,Ligands ,Lymphocyte Activation ,Biochemistry ,0302 clinical medicine ,Molecular Cell Biology ,CRYSTAL-STRUCTURE ,Membrane Receptor Signaling ,lcsh:Science ,Receptor ,IMMUNE SYNAPSES ,Immune Response ,0303 health sciences ,Immune System Proteins ,Microscopy, Confocal ,Multidisciplinary ,Immune cells ,Signaling in Selected Disciplines ,Cell biology ,Multidisciplinary Sciences ,Killer Cells, Natural ,medicine.anatomical_structure ,NK Cell Lectin-Like Receptor Subfamily K ,B-CELLS ,Receptors, KIR2DL1 ,Science & Technology - Other Topics ,Signal transduction ,Immunologic Receptor Signaling ,Research Article ,Signal Transduction ,Protein Binding ,General Science & Technology ,Recombinant Fusion Proteins ,Immunology ,Molecular Sequence Data ,HLA-C Antigens ,Biology ,Immunological Signaling ,Cell Line ,Immune Activation ,03 medical and health sciences ,Immune system ,KIR2DL1 ,MD Multidisciplinary ,medicine ,Humans ,Amino Acid Sequence ,030304 developmental biology ,Science & Technology ,lcsh:R ,Histocompatibility Antigens Class I ,Immunity ,Proteins ,Immunoregulation ,NKG2D ,QP ,MHC CLASS-I ,Luminescent Proteins ,stomatognathic diseases ,Cell culture ,T-CELLS ,TARGET-CELLS ,lcsh:Q ,LIGAND ,030215 immunology - Abstract
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.
- Published
- 2010
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