'Unlicensed' natural killer cells dominate the response to cytomegalovirus infection

Mark T. Orr, William J Murphy, Lewis L. Lanier

Research output: Contribution to journalArticlepeer-review

197 Scopus citations


Natural killer (NK) cells expressing inhibitory receptors that bind to self major histocompatibility complex (MHC) class I are 'licensed', or rendered functionally more responsive to stimulation, whereas 'unlicensed' NK cells lacking receptors for self MHC class I are hyporesponsive. Here we show that contrary to the licensing hypothesis, unlicensed NK cells were the main mediators of NK cell-mediated control of mouse cytomegalovirus infection in vivo. Depletion of unlicensed NK cells impaired control of viral titers, but depletion of licensed NK cells did not. The transfer of unlicensed NK cells was more protective than was the transfer of licensed NK cells. Signaling by the tyrosine phosphatase SHP-1 limited the proliferation of licensed NK cells but not that of unlicensed NK cells during infection. Thus, unlicensed NK cells are critical for protection against viral infection.

Original languageEnglish (US)
Pages (from-to)321-327
Number of pages7
JournalNature Immunology
Issue number4
StatePublished - 2010

ASJC Scopus subject areas

  • Immunology


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