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Effects of peptide on NK cell-mediated MHC I recognition

Effects of peptide on NK cell-mediated MHC I recognition
Effects of peptide on NK cell-mediated MHC I recognition
The inhibitory receptors for MHC class I have a central role in controlling natural killer (NK) cell activity. Soon after their discovery, it was found that these receptors have a degree of peptide selectivity. Such peptide selectivity has been demonstrated for all inhibitory killer cell immunoglobulin-like receptor (KIR) tested to date, certain activating KIR, and also members of the C-type lectin-like family of receptors. This selectivity is much broader than the peptide specificity of T cell receptors, with NK cell receptors recognizing peptide motifs, rather than individual peptides. Inhibitory receptors on NK cells can survey the peptide:MHC complexes expressed on the surface of target cells, therefore subsequent transduction of an inhibitory signal depends on the overall peptide content of these MHC class I complexes. Functionally, KIR-expressing NK cells have been shown to be unexpectedly sensitive to changes in the peptide content of MHC class I, as peptide:MHC class I complexes that weakly engage KIR can antagonize the inhibitory signals generated by engagement of stronger KIR-binding peptide:MHC class I complexes. This property provides KIR-expressing NK cells with the potential to recognize changes in the peptide:MHC class I repertoire, which may occur during viral infections and tumorigenesis. By contrast, in the presence of HLA class I leader peptides, virus-derived peptides can induce a synergistic inhibition of CD94:NKG2A-expressing NK cells through recruitment of CD94 in the absence of NKG2A. On the other hand, CD94:NKG2A-positive NK cells can be exquisitely sensitive to changes in the levels of MHC class I. Peptide antagonism and sensitivity to changes in MHC class I levels are properties that distinguish KIR and CD94:NKG2A. The subtle difference in the properties of NK cells expressing these receptors provides a rationale for having complementary inhibitory receptor systems for MHC class I.
1664-3224
1-8
Cassidy, S.A.
0abada2d-d4d0-42d9-a55e-097960a0b3fa
Cheent, K.S.
9a9711a0-aad0-413d-a23f-a689ca547597
Khakoo, S.I.
6c16d2f5-ae80-4d9b-9100-6bfb34ad0273
Cassidy, S.A.
0abada2d-d4d0-42d9-a55e-097960a0b3fa
Cheent, K.S.
9a9711a0-aad0-413d-a23f-a689ca547597
Khakoo, S.I.
6c16d2f5-ae80-4d9b-9100-6bfb34ad0273

Cassidy, S.A., Cheent, K.S. and Khakoo, S.I. (2014) Effects of peptide on NK cell-mediated MHC I recognition. Frontiers in Immunology, 5 (133), 1-8. (doi:10.3389/fimmu.2014.00133). (PMID:24744756)

Record type: Article

Abstract

The inhibitory receptors for MHC class I have a central role in controlling natural killer (NK) cell activity. Soon after their discovery, it was found that these receptors have a degree of peptide selectivity. Such peptide selectivity has been demonstrated for all inhibitory killer cell immunoglobulin-like receptor (KIR) tested to date, certain activating KIR, and also members of the C-type lectin-like family of receptors. This selectivity is much broader than the peptide specificity of T cell receptors, with NK cell receptors recognizing peptide motifs, rather than individual peptides. Inhibitory receptors on NK cells can survey the peptide:MHC complexes expressed on the surface of target cells, therefore subsequent transduction of an inhibitory signal depends on the overall peptide content of these MHC class I complexes. Functionally, KIR-expressing NK cells have been shown to be unexpectedly sensitive to changes in the peptide content of MHC class I, as peptide:MHC class I complexes that weakly engage KIR can antagonize the inhibitory signals generated by engagement of stronger KIR-binding peptide:MHC class I complexes. This property provides KIR-expressing NK cells with the potential to recognize changes in the peptide:MHC class I repertoire, which may occur during viral infections and tumorigenesis. By contrast, in the presence of HLA class I leader peptides, virus-derived peptides can induce a synergistic inhibition of CD94:NKG2A-expressing NK cells through recruitment of CD94 in the absence of NKG2A. On the other hand, CD94:NKG2A-positive NK cells can be exquisitely sensitive to changes in the levels of MHC class I. Peptide antagonism and sensitivity to changes in MHC class I levels are properties that distinguish KIR and CD94:NKG2A. The subtle difference in the properties of NK cells expressing these receptors provides a rationale for having complementary inhibitory receptor systems for MHC class I.

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Accepted/In Press date: 17 March 2014
Published date: 31 March 2014
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 390134
URI: https://eprints.soton.ac.uk/id/eprint/390134
ISSN: 1664-3224
PURE UUID: be4236f2-0c2a-425c-9732-bf7ccb6be662

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Date deposited: 18 Mar 2016 16:58
Last modified: 17 Jul 2017 19:30

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