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KIR2DS2 recognizes conserved peptides derived from viral helicases in the context of HLA-C

KIR2DS2 recognizes conserved peptides derived from viral helicases in the context of HLA-C
KIR2DS2 recognizes conserved peptides derived from viral helicases in the context of HLA-C
Killer cell immunoglobulin-like receptors (KIR) are rapidly evolving species-specific natural killer cell receptors associated with protection against multiple different human viral infections. We report that the activating receptor KIR2DS2 directly recognizes viral peptides derived from conserved regions of flaviviral superfamily 2 RNA helicases in the context of MHC class I. The peptide LNPSVAATL, from the HCV helicase, binds HLA-C*0102 leading to NK cell activation through engagement of KIR2DS2. Similarly, HLA-C*0102 presents
highly conserved peptides from the helicase motif 1b region of related flaviviruses, including dengue, Zika, yellow fever and Japanese encephalitis viruses, to KIR2DS2. These flaviviral peptides all contain an “MCHAT” motif, which is present in 61 out of 63 flaviviruses. LNPSVAATL is also highly conserved across HCV genotypes and mutation of this epitope is poorly tolerated by HCV. KIR2DS2 recognizes endogenously presented helicase peptides and KIR2DS2 is sufficient to inhibit HCV and dengue virus replication in the context of HLAC*
0102. Targeting short, but highly conserved, viral peptides provide non-rearranging innate immune receptors with an efficient mechanism to recognize multiple, highly variable pathogenic RNA viruses.
Naiyer, Mohammed M.
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Cassidy, Sorcha A.
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Magri, Andrea
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Cowton, Vanessa
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Chen, Kevin
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Mansour, Salah
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Kranidioti, Charikleia
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Mbiribindi, Berenice
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Rettman, Pauline
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Harris, Scott
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Fanning, Liam J.
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Mulder, Arend
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Claas, Franz H.J.
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Davidson, Andrew D.
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Patel, Arvind H.
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Purbhoo, Marco A.
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Khakoo, Salim I.
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Naiyer, Mohammed M.
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Cassidy, Sorcha A.
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Magri, Andrea
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Cowton, Vanessa
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Chen, Kevin
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Mansour, Salah
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Kranidioti, Charikleia
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Mbiribindi, Berenice
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Rettman, Pauline
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Harris, Scott
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Fanning, Liam J.
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Mulder, Arend
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Claas, Franz H.J.
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Davidson, Andrew D.
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Patel, Arvind H.
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Purbhoo, Marco A.
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Khakoo, Salim I.
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Naiyer, Mohammed M., Cassidy, Sorcha A., Magri, Andrea, Cowton, Vanessa, Chen, Kevin, Mansour, Salah, Kranidioti, Charikleia, Mbiribindi, Berenice, Rettman, Pauline, Harris, Scott, Fanning, Liam J., Mulder, Arend, Claas, Franz H.J., Davidson, Andrew D., Patel, Arvind H., Purbhoo, Marco A. and Khakoo, Salim I. (2017) KIR2DS2 recognizes conserved peptides derived from viral helicases in the context of HLA-C. Science immunology, 2 (15). (doi:10.1126/sciimmunol.aal5296).

Record type: Article

Abstract

Killer cell immunoglobulin-like receptors (KIR) are rapidly evolving species-specific natural killer cell receptors associated with protection against multiple different human viral infections. We report that the activating receptor KIR2DS2 directly recognizes viral peptides derived from conserved regions of flaviviral superfamily 2 RNA helicases in the context of MHC class I. The peptide LNPSVAATL, from the HCV helicase, binds HLA-C*0102 leading to NK cell activation through engagement of KIR2DS2. Similarly, HLA-C*0102 presents
highly conserved peptides from the helicase motif 1b region of related flaviviruses, including dengue, Zika, yellow fever and Japanese encephalitis viruses, to KIR2DS2. These flaviviral peptides all contain an “MCHAT” motif, which is present in 61 out of 63 flaviviruses. LNPSVAATL is also highly conserved across HCV genotypes and mutation of this epitope is poorly tolerated by HCV. KIR2DS2 recognizes endogenously presented helicase peptides and KIR2DS2 is sufficient to inhibit HCV and dengue virus replication in the context of HLAC*
0102. Targeting short, but highly conserved, viral peptides provide non-rearranging innate immune receptors with an efficient mechanism to recognize multiple, highly variable pathogenic RNA viruses.

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KIR2DS2 2017 AM - Accepted Manuscript
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Accepted/In Press date: 1 September 2017
e-pub ahead of print date: 15 September 2017
Published date: 22 September 2017

Identifiers

Local EPrints ID: 414342
URI: https://eprints.soton.ac.uk/id/eprint/414342
PURE UUID: 245a1646-2075-4c65-ac68-350acae9b8b1
ORCID for Mohammed M. Naiyer: ORCID iD orcid.org/0000-0002-4441-311X
ORCID for Salah Mansour: ORCID iD orcid.org/0000-0002-5982-734X

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Date deposited: 26 Sep 2017 16:30
Last modified: 10 Dec 2019 01:41

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Contributors

Author: Mohammed M. Naiyer ORCID iD
Author: Sorcha A. Cassidy
Author: Andrea Magri
Author: Vanessa Cowton
Author: Kevin Chen
Author: Salah Mansour ORCID iD
Author: Charikleia Kranidioti
Author: Berenice Mbiribindi
Author: Pauline Rettman
Author: Scott Harris
Author: Liam J. Fanning
Author: Arend Mulder
Author: Franz H.J. Claas
Author: Andrew D. Davidson
Author: Arvind H. Patel
Author: Marco A. Purbhoo
Author: Salim I. Khakoo

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