KIR2DS1-mediated activation overrides NKG2A-mediated inhibition in HLA-C C2-negative individuals

B. Foley, D. De Santis, Louise Lathbury, Frank Christiansen, C. Witt

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

NK cell cytotoxicity is controlled through a balance of both activating and inhibitory signals. The HLA specificity of alloreactive NK cells has been previously shown to be controlled by inhibitory killer immunoglobulin-like receptors (KIRs). Alloreactive NK cells lyse targets that lack the HLA ligand for their inhibitory KIR. We have characterized in detail an alloreactive NK clone in which the specificity is controlled by an activating receptor, KIR2DS1. Only target cells expressing the HLA-C group 2 (C2) epitope were lysed by this clone and homozygous C2 targets were lysed more strongly than heterozygous C1/C2 targets. Anti-CD158a (KIR2DS1) blocked lysis of targets confirming KIR2DS1 was responsible. Although this NK clone expressed NKG2A, an inhibitory receptor whose ligand is HLA-E, targets with ligands for both KIR2DS1 and NKG2A were lysed by this clone indicating that the KIR2DS1-mediated activation signal overrides the NKG2A-mediated inhibitory signal. KIR2DS1 activated NK clones in polyclonally expanded NK cultures from a donor that lacked the C2 epitope accounted for similar to 1% of all NK cells. This study highlights a potential role for NK cells controlled by activating KIR in mediating NK alloreactivity.
Original languageEnglish
Pages (from-to)555-563
JournalInternational Immunology
Volume20
Issue number4
DOIs
Publication statusPublished - 2008

Fingerprint

HLA-C Antigens
Natural Killer Cells
KIR Receptors
Clone Cells
Ligands
Epitopes
NK Cell Lectin-Like Receptor Subfamily C

Cite this

Foley, B. ; De Santis, D. ; Lathbury, Louise ; Christiansen, Frank ; Witt, C. / KIR2DS1-mediated activation overrides NKG2A-mediated inhibition in HLA-C C2-negative individuals. In: International Immunology. 2008 ; Vol. 20, No. 4. pp. 555-563.
@article{bf7cf6d8f2364a9c947ac2fa0e4555a9,
title = "KIR2DS1-mediated activation overrides NKG2A-mediated inhibition in HLA-C C2-negative individuals",
abstract = "NK cell cytotoxicity is controlled through a balance of both activating and inhibitory signals. The HLA specificity of alloreactive NK cells has been previously shown to be controlled by inhibitory killer immunoglobulin-like receptors (KIRs). Alloreactive NK cells lyse targets that lack the HLA ligand for their inhibitory KIR. We have characterized in detail an alloreactive NK clone in which the specificity is controlled by an activating receptor, KIR2DS1. Only target cells expressing the HLA-C group 2 (C2) epitope were lysed by this clone and homozygous C2 targets were lysed more strongly than heterozygous C1/C2 targets. Anti-CD158a (KIR2DS1) blocked lysis of targets confirming KIR2DS1 was responsible. Although this NK clone expressed NKG2A, an inhibitory receptor whose ligand is HLA-E, targets with ligands for both KIR2DS1 and NKG2A were lysed by this clone indicating that the KIR2DS1-mediated activation signal overrides the NKG2A-mediated inhibitory signal. KIR2DS1 activated NK clones in polyclonally expanded NK cultures from a donor that lacked the C2 epitope accounted for similar to 1{\%} of all NK cells. This study highlights a potential role for NK cells controlled by activating KIR in mediating NK alloreactivity.",
author = "B. Foley and {De Santis}, D. and Louise Lathbury and Frank Christiansen and C. Witt",
year = "2008",
doi = "10.1093/intimm/dxn013",
language = "English",
volume = "20",
pages = "555--563",
journal = "International Immunology",
issn = "0953-8178",
publisher = "OXFORD UNIV PRESS UNITED KINGDOM",
number = "4",

}

KIR2DS1-mediated activation overrides NKG2A-mediated inhibition in HLA-C C2-negative individuals. / Foley, B.; De Santis, D.; Lathbury, Louise; Christiansen, Frank; Witt, C.

In: International Immunology, Vol. 20, No. 4, 2008, p. 555-563.

Research output: Contribution to journalArticle

TY - JOUR

T1 - KIR2DS1-mediated activation overrides NKG2A-mediated inhibition in HLA-C C2-negative individuals

AU - Foley, B.

AU - De Santis, D.

AU - Lathbury, Louise

AU - Christiansen, Frank

AU - Witt, C.

PY - 2008

Y1 - 2008

N2 - NK cell cytotoxicity is controlled through a balance of both activating and inhibitory signals. The HLA specificity of alloreactive NK cells has been previously shown to be controlled by inhibitory killer immunoglobulin-like receptors (KIRs). Alloreactive NK cells lyse targets that lack the HLA ligand for their inhibitory KIR. We have characterized in detail an alloreactive NK clone in which the specificity is controlled by an activating receptor, KIR2DS1. Only target cells expressing the HLA-C group 2 (C2) epitope were lysed by this clone and homozygous C2 targets were lysed more strongly than heterozygous C1/C2 targets. Anti-CD158a (KIR2DS1) blocked lysis of targets confirming KIR2DS1 was responsible. Although this NK clone expressed NKG2A, an inhibitory receptor whose ligand is HLA-E, targets with ligands for both KIR2DS1 and NKG2A were lysed by this clone indicating that the KIR2DS1-mediated activation signal overrides the NKG2A-mediated inhibitory signal. KIR2DS1 activated NK clones in polyclonally expanded NK cultures from a donor that lacked the C2 epitope accounted for similar to 1% of all NK cells. This study highlights a potential role for NK cells controlled by activating KIR in mediating NK alloreactivity.

AB - NK cell cytotoxicity is controlled through a balance of both activating and inhibitory signals. The HLA specificity of alloreactive NK cells has been previously shown to be controlled by inhibitory killer immunoglobulin-like receptors (KIRs). Alloreactive NK cells lyse targets that lack the HLA ligand for their inhibitory KIR. We have characterized in detail an alloreactive NK clone in which the specificity is controlled by an activating receptor, KIR2DS1. Only target cells expressing the HLA-C group 2 (C2) epitope were lysed by this clone and homozygous C2 targets were lysed more strongly than heterozygous C1/C2 targets. Anti-CD158a (KIR2DS1) blocked lysis of targets confirming KIR2DS1 was responsible. Although this NK clone expressed NKG2A, an inhibitory receptor whose ligand is HLA-E, targets with ligands for both KIR2DS1 and NKG2A were lysed by this clone indicating that the KIR2DS1-mediated activation signal overrides the NKG2A-mediated inhibitory signal. KIR2DS1 activated NK clones in polyclonally expanded NK cultures from a donor that lacked the C2 epitope accounted for similar to 1% of all NK cells. This study highlights a potential role for NK cells controlled by activating KIR in mediating NK alloreactivity.

U2 - 10.1093/intimm/dxn013

DO - 10.1093/intimm/dxn013

M3 - Article

VL - 20

SP - 555

EP - 563

JO - International Immunology

JF - International Immunology

SN - 0953-8178

IS - 4

ER -