title: Peptide antagonism as a mechanism for NK cell activation.
abstract: Inhibition of natural killer (NK) cells is mediated by MHC class I receptors including the killer cell Ig-like receptor (KIR). We demonstrate that HLA-C binding peptides can function as altered peptide ligands for KIR and antagonize the inhibition mediated by KIR2DL2/KIR2DL3. Antagonistic peptides promote clustering of KIR at the interface of effector and target cells, but do not result in inhibition of NK cells. Our data show that, as for T cells, small changes in the peptide content of MHC class I can regulate NK cell activity.
authors.affiliation: Divisions of Medicine and Cell and Molecular Medicine, Imperial College London, London W2 1PG, United Kingdom.
authors.forename: Lena
authors.initials: L
authors.lastname: Fadda
authors.forename: Gwenoline
authors.initials: G
authors.lastname: Borhis
authors.forename: Parvin
authors.initials: P
authors.lastname: Ahmed
authors.forename: Kuldeep
authors.initials: K
authors.lastname: Cheent
authors.forename: Sophie V
authors.initials: SV
authors.lastname: Pageon
authors.forename: Angelica
authors.initials: A
authors.lastname: Cazaly
authors.forename: Stavros
authors.initials: S
authors.lastname: Stathopoulos
authors.forename: Derek
authors.initials: D
authors.lastname: Middleton
authors.forename: Arend
authors.initials: A
authors.lastname: Mulder
authors.forename: Frans H J
authors.initials: FH
authors.lastname: Claas
authors.forename: Tim
authors.initials: T
authors.lastname: Elliott
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Davis
authors.forename: Marco A
authors.initials: MA
authors.lastname: Purbhoo
authors.forename: Salim I
authors.initials: SI
authors.lastname: Khakoo
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D015236:HLA-C Antigens / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D007700:Kinetics; D008024:Ligands; D008213:Lymphocyte Activation; D009842:Oligopeptides / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D051567:Proto-Oncogene Proteins c-vav / Q000378:metabolism; D054340:Receptors, KIR / Q000037:antagonists & inhibitors / Q000276:immunology; D054343:Receptors, KIR2DL2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D054344:Receptors, KIR2DL3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D015236:HLA-C Antigens; C515077:KIR2DL2 protein, human; C515078:KIR2DL3 protein, human; D008024:Ligands; D009842:Oligopeptides; D051567:Proto-Oncogene Proteins c-vav; D054340:Receptors, KIR; D054343:Receptors, KIR2DL2; D054344:Receptors, KIR2DL3; C496618:VAV1 protein, human