title: A peptide antagonist disrupts NK cell inhibitory synapse formation.
abstract: Productive engagement of MHC class I by inhibitory NK cell receptors depends on the peptide bound by the MHC class I molecule. Peptide:MHC complexes that bind weakly to killer cell Ig-like receptors (KIRs) can antagonize the inhibition mediated by high-affinity peptide:MHC complexes and cause NK cell activation. We show that low-affinity peptide:MHC complexes stall inhibitory signaling at the step of Src homology protein tyrosine phosphatase 1 recruitment and do not go on to form the KIR microclusters induced by high-affinity peptide:MHC, which are associated with Vav dephosphorylation and downstream signaling. Furthermore, the low-affinity peptide:MHC complexes prevented the formation of KIR microclusters by high-affinity peptide:MHC. Thus, peptide antagonism of NK cells is an active phenomenon of inhibitory synapse disruption.
authors: Division of Medicine, Imperial College London, London SW7 2AZ, United Kingdom.
authors: Gwenoline
authors: G
authors: Borhis
authors: Parvin S
authors: PS
authors: Ahmed
authors: Bérénice
authors: B
authors: Mbiribindi
authors: Mohammed M
authors: MM
authors: Naiyer
authors: Daniel M
authors: DM
authors: Davis
authors: Marco A
authors: MA
authors: Purbhoo
authors: Salim I
authors: SI
authors: Khakoo
mesh_terms: D002460:Cell Line; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D009154:Mutation; D010455:Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010649:Phenylalanine / Q000235:genetics; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D054344:Receptors, KIR2DL3 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013569:Synapses / Q000276:immunology* / Q000378:metabolism
chemical_list: C515078:KIR2DL3 protein, human; D010455:Peptides; D054344:Receptors, KIR2DL3; D010649:Phenylalanine
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