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Synergistic inhibition of natural killer cells by the nonsignaling molecule CD94

Synergistic inhibition of natural killer cells by the nonsignaling molecule CD94
Synergistic inhibition of natural killer cells by the nonsignaling molecule CD94
Peptide selectivity is a feature of inhibitory receptors for MHC class I expressed by natural killer (NK) cells. CD94–NKG2A operates in tandem with the polymorphic killer cell Ig-like receptors (KIR) and Ly49 systems to inhibit NK cells. However, the benefits of having two distinct inhibitory receptor–ligand systems are not clear. We show that noninhibitory peptides presented by HLA-E can augment the inhibition of NKG2A+ NK cells mediated by MHC class I signal peptides through the engagement of CD94 without a signaling partner. Thus, CD94 is a peptide-selective NK cell receptor, and NK cells can be regulated by nonsignaling interactions. We also show that KIR+ and NKG2A+ NK cells respond with differing stoichiometries to MHC class I down-regulation. MHC-I–bound peptide functions as a molecular rheostat controlling NK cell function. Selected peptides which in isolation do not inhibit NK cells can have different effects on KIR and NKG2A receptors. Thus, these two inhibitory systems may complement each other by having distinct responses to bound peptide and surface levels of MHC class I.
Histocompatibility Antigens Class I, Humans, Jurkat Cells, Killer Cells, Natural, Lymphocyte Activation, NK Cell Lectin-Like Receptor Subfamily C, NK Cell Lectin-Like Receptor Subfamily D, Peptides, Receptors, KIR, Journal Article, Research Support, Non-U.S. Gov't
0027-8424
16981-16986
Cheent, Kuldeep S.
b8054563-cd72-456d-b165-bf55bc94af3c
Jamil, Khaleel M.
ad7bdf43-3296-4459-a615-1a0aca5f36ff
Cassidy, Sorcha
f1f3fe00-a357-4ad1-a0e8-d86f2c3b0502
Liu, Mengya
24e44729-d719-4c97-aa3d-cb20f9107ca1
Mbiribindi, Berenice
0f654cae-3ba2-42f3-93ec-0da44b5ada19
Mulder, Arend
caf04be4-7be4-4cec-9a7b-32638c7a3688
Claas, Frans H.J.
11a3dc77-f915-4086-b7f4-b8632f998cb3
Purbhoo, Marco A.
990498b1-eb64-406b-875a-181e9ffd94df
Khakoo, Salim I.
6c16d2f5-ae80-4d9b-9100-6bfb34ad0273
Cheent, Kuldeep S.
b8054563-cd72-456d-b165-bf55bc94af3c
Jamil, Khaleel M.
ad7bdf43-3296-4459-a615-1a0aca5f36ff
Cassidy, Sorcha
f1f3fe00-a357-4ad1-a0e8-d86f2c3b0502
Liu, Mengya
24e44729-d719-4c97-aa3d-cb20f9107ca1
Mbiribindi, Berenice
0f654cae-3ba2-42f3-93ec-0da44b5ada19
Mulder, Arend
caf04be4-7be4-4cec-9a7b-32638c7a3688
Claas, Frans H.J.
11a3dc77-f915-4086-b7f4-b8632f998cb3
Purbhoo, Marco A.
990498b1-eb64-406b-875a-181e9ffd94df
Khakoo, Salim I.
6c16d2f5-ae80-4d9b-9100-6bfb34ad0273

Cheent, Kuldeep S., Jamil, Khaleel M., Cassidy, Sorcha, Liu, Mengya, Mbiribindi, Berenice, Mulder, Arend, Claas, Frans H.J., Purbhoo, Marco A. and Khakoo, Salim I. (2013) Synergistic inhibition of natural killer cells by the nonsignaling molecule CD94. Proceedings of the National Academy of Sciences, 110 (42), 16981-16986. (doi:10.1073/pnas.1304366110).

Record type: Article

Abstract

Peptide selectivity is a feature of inhibitory receptors for MHC class I expressed by natural killer (NK) cells. CD94–NKG2A operates in tandem with the polymorphic killer cell Ig-like receptors (KIR) and Ly49 systems to inhibit NK cells. However, the benefits of having two distinct inhibitory receptor–ligand systems are not clear. We show that noninhibitory peptides presented by HLA-E can augment the inhibition of NKG2A+ NK cells mediated by MHC class I signal peptides through the engagement of CD94 without a signaling partner. Thus, CD94 is a peptide-selective NK cell receptor, and NK cells can be regulated by nonsignaling interactions. We also show that KIR+ and NKG2A+ NK cells respond with differing stoichiometries to MHC class I down-regulation. MHC-I–bound peptide functions as a molecular rheostat controlling NK cell function. Selected peptides which in isolation do not inhibit NK cells can have different effects on KIR and NKG2A receptors. Thus, these two inhibitory systems may complement each other by having distinct responses to bound peptide and surface levels of MHC class I.

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More information

e-pub ahead of print date: 30 September 2013
Published date: 15 October 2013
Keywords: Histocompatibility Antigens Class I, Humans, Jurkat Cells, Killer Cells, Natural, Lymphocyte Activation, NK Cell Lectin-Like Receptor Subfamily C, NK Cell Lectin-Like Receptor Subfamily D, Peptides, Receptors, KIR, Journal Article, Research Support, Non-U.S. Gov't
Organisations: Tissue Infection & Repair, Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 359583
URI: https://eprints.soton.ac.uk/id/eprint/359583
ISSN: 0027-8424
PURE UUID: 843b6ba9-b923-4a23-9669-2ca6258c0242

Catalogue record

Date deposited: 05 Nov 2013 09:57
Last modified: 16 Jul 2019 21:18

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