A role for MHC class I down-regulation in NK cell lysis of herpes virus-infected cells

Bertrand Huard, Klaus Frueh

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

NK cells represent an efficient first line of defense against virus infection, preceding the generation of adaptive T cell responses. However, the NK cell receptors involved in the recognition of virus-infected cells remain ill defined. We studied the in vitro response of isolated human NK cell clones to cells infected by the herpes viruses, herpes simplex virus (HSV) and human cytomegalovirus (HCMV). Both HSV and HCMV were found to induce NK cell cytotoxicity by down-regulating HLA-C molecules engaged in the triggering of killer inhibitory receptors (KIR). This conclusion was further substantiated by the finding that expression of viral genes known to interfere with MHC class I expression, such as the TAP inhibitor ICP47 of HSV and the MHC class I-destroying US11 protein of HCMV, was sufficient to trigger the cytotoxicity of NK cell clones expressing an inhibitory KIR for HLA-C. These results show for the first time that MHC class I down-regulation could render cells infected with herpes viruses susceptible to NK cell killing, thus demonstrating a role for KIR in the recognition of virally infected cells.

Original languageEnglish (US)
Pages (from-to)509-515
Number of pages7
JournalEuropean Journal of Immunology
Volume30
Issue number2
DOIs
StatePublished - 2000
Externally publishedYes

Fingerprint

Natural Killer Cells
KIR Receptors
Down-Regulation
Viruses
Simplexvirus
HLA-C Antigens
Cytomegalovirus
Clone Cells
Natural Killer Cell Receptors
Viral Genes
Virus Diseases
T-Lymphocytes

Keywords

  • Herpes virus
  • Killer inhibitory receptor
  • MHC class I
  • NK cell

ASJC Scopus subject areas

  • Immunology

Cite this

A role for MHC class I down-regulation in NK cell lysis of herpes virus-infected cells. / Huard, Bertrand; Frueh, Klaus.

In: European Journal of Immunology, Vol. 30, No. 2, 2000, p. 509-515.

Research output: Contribution to journalArticle

@article{07c33dffbf844f838849995d44b33d84,
title = "A role for MHC class I down-regulation in NK cell lysis of herpes virus-infected cells",
abstract = "NK cells represent an efficient first line of defense against virus infection, preceding the generation of adaptive T cell responses. However, the NK cell receptors involved in the recognition of virus-infected cells remain ill defined. We studied the in vitro response of isolated human NK cell clones to cells infected by the herpes viruses, herpes simplex virus (HSV) and human cytomegalovirus (HCMV). Both HSV and HCMV were found to induce NK cell cytotoxicity by down-regulating HLA-C molecules engaged in the triggering of killer inhibitory receptors (KIR). This conclusion was further substantiated by the finding that expression of viral genes known to interfere with MHC class I expression, such as the TAP inhibitor ICP47 of HSV and the MHC class I-destroying US11 protein of HCMV, was sufficient to trigger the cytotoxicity of NK cell clones expressing an inhibitory KIR for HLA-C. These results show for the first time that MHC class I down-regulation could render cells infected with herpes viruses susceptible to NK cell killing, thus demonstrating a role for KIR in the recognition of virally infected cells.",
keywords = "Herpes virus, Killer inhibitory receptor, MHC class I, NK cell",
author = "Bertrand Huard and Klaus Frueh",
year = "2000",
doi = "10.1002/1521-4141(200002)30:2<509::AID-IMMU509>3.0.CO;2-H",
language = "English (US)",
volume = "30",
pages = "509--515",
journal = "European Journal of Immunology",
issn = "0014-2980",
publisher = "Wiley-VCH Verlag",
number = "2",

}

TY - JOUR

T1 - A role for MHC class I down-regulation in NK cell lysis of herpes virus-infected cells

AU - Huard, Bertrand

AU - Frueh, Klaus

PY - 2000

Y1 - 2000

N2 - NK cells represent an efficient first line of defense against virus infection, preceding the generation of adaptive T cell responses. However, the NK cell receptors involved in the recognition of virus-infected cells remain ill defined. We studied the in vitro response of isolated human NK cell clones to cells infected by the herpes viruses, herpes simplex virus (HSV) and human cytomegalovirus (HCMV). Both HSV and HCMV were found to induce NK cell cytotoxicity by down-regulating HLA-C molecules engaged in the triggering of killer inhibitory receptors (KIR). This conclusion was further substantiated by the finding that expression of viral genes known to interfere with MHC class I expression, such as the TAP inhibitor ICP47 of HSV and the MHC class I-destroying US11 protein of HCMV, was sufficient to trigger the cytotoxicity of NK cell clones expressing an inhibitory KIR for HLA-C. These results show for the first time that MHC class I down-regulation could render cells infected with herpes viruses susceptible to NK cell killing, thus demonstrating a role for KIR in the recognition of virally infected cells.

AB - NK cells represent an efficient first line of defense against virus infection, preceding the generation of adaptive T cell responses. However, the NK cell receptors involved in the recognition of virus-infected cells remain ill defined. We studied the in vitro response of isolated human NK cell clones to cells infected by the herpes viruses, herpes simplex virus (HSV) and human cytomegalovirus (HCMV). Both HSV and HCMV were found to induce NK cell cytotoxicity by down-regulating HLA-C molecules engaged in the triggering of killer inhibitory receptors (KIR). This conclusion was further substantiated by the finding that expression of viral genes known to interfere with MHC class I expression, such as the TAP inhibitor ICP47 of HSV and the MHC class I-destroying US11 protein of HCMV, was sufficient to trigger the cytotoxicity of NK cell clones expressing an inhibitory KIR for HLA-C. These results show for the first time that MHC class I down-regulation could render cells infected with herpes viruses susceptible to NK cell killing, thus demonstrating a role for KIR in the recognition of virally infected cells.

KW - Herpes virus

KW - Killer inhibitory receptor

KW - MHC class I

KW - NK cell

UR - http://www.scopus.com/inward/record.url?scp=0342948593&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0342948593&partnerID=8YFLogxK

U2 - 10.1002/1521-4141(200002)30:2<509::AID-IMMU509>3.0.CO;2-H

DO - 10.1002/1521-4141(200002)30:2<509::AID-IMMU509>3.0.CO;2-H

M3 - Article

C2 - 10671206

AN - SCOPUS:0342948593

VL - 30

SP - 509

EP - 515

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

IS - 2

ER -