Peptide antagonism as a mechanism for NK cell activation.
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.
Fadda
Lena
L
Divisions of Medicine and Cell and Molecular Medicine, Imperial College London, London W2 1PG, United Kingdom.
Borhis
Gwenoline
G
Ahmed
Parvin
P
Cheent
Kuldeep
K
Pageon
Sophie V
SV
Cazaly
Angelica
A
Stathopoulos
Stavros
S
Middleton
Derek
D
Mulder
Arend
A
Claas
Frans H J
FH
Elliott
Tim
T
Davis
Daniel M
DM
Purbhoo
Marco A
MA
Khakoo
Salim I
SI
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
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