title: KIR enrichment at the effector-target cell interface is more sensitive than signaling to the strength of ligand binding.
abstract: Target cell lysis by natural killer cells is inhibited by killer cell immunoglobulin-like receptors (KIR) that bind major histocompatibility complex class I molecules. Many lymphocyte receptors, including KIR, become enriched at the interface with ligand-bearing cells. The contribution of the enrichment to inhibitory signaling has not been determined. We now describe a KIR variant with enhanced green fluorescent protein (EGFP) at the N terminus that can mediate inhibitory signaling, but its enrichment is markedly reduced. This receptor is only slightly weaker at inhibiting lysis than the same KIR tagged with EGFP in the cytoplasmic tail, even though the latter enriched as extensively as wild-type KIR. A slight defect was also detected in the ability of the receptor to reduce adhesion to target cells and for binding of a soluble counterpart to cell surface HLA-C. Our findings suggest that the strength of the interaction required to readily detect receptor enrichment exceeds that required for signaling.
authors.affiliation: Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Borszcz
authors.forename: Mary
authors.initials: M
authors.lastname: Peterson
authors.forename: Leah
authors.initials: L
authors.lastname: Standeven
authors.forename: Sheryl
authors.initials: S
authors.lastname: Kirwan
authors.forename: Mina
authors.initials: M
authors.lastname: Sandusky
authors.forename: Andrew
authors.initials: A
authors.lastname: Shaw
authors.forename: Eric O
authors.initials: EO
authors.lastname: Long
authors.forename: Deborah N
authors.initials: DN
authors.lastname: Burshtyn
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D049452:Green Fluorescent Proteins; D007694:Killer Cells, Natural / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D007700:Kinetics; D008024:Ligands; D008164:Luminescent Proteins / Q000235:genetics; D011971:Receptors, Immunologic / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D054340:Receptors, KIR; D011993:Recombinant Fusion Proteins / Q000032:analysis; D015398:Signal Transduction; D015032:Zinc / Q000494:pharmacology
chemical_list: D008024:Ligands; D008164:Luminescent Proteins; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D015032:Zinc