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

Bertrand Huard, Klaus Früh

Research output: Contribution to journalArticlepeer-review

59 Scopus citations


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
Issue number2
StatePublished - 2000
Externally publishedYes


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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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