Ly49P recognition of cytomegalovirus-infected cells expressing H2-D k and CMV-encoded m04 correlates with the NK cell antiviral response

Agnieszka Kielczewska, Michal Pyzik, Tianhe Sun, Astrid Krmpotic, Melissa B. Lodoen, Michael W. Munks, Marina Babic, Ann B. Hill, Ulrich H. Koszinowski, Stipan Jonjic, Lewis L. Lanier, Silvia M. Vidal

Research output: Contribution to journalArticle

94 Scopus citations

Abstract

Natural killer (NK) cells are crucial in resistance to certain viral infections, but the mechanisms used to recognize infected cells remain largely unknown. Here, we show that the activating Ly49P receptor recognizes cells infected with mouse cytomegalovirus (MCMV) by a process that requires the presence of H2-D k and the MCMV m04 protein. Using H2 chimeras between H2-D b and -D k, we demonstrate that the H2-D k peptide-binding platform is required for Ly49P recognition. We identified m04 as a viral component necessary for recognition using a panel of MCMV-deletion mutant viruses and complementation ofm04-deletion mutant (δm04) virus infection. MA/My mice, which express Ly49P and H2- D k, are resistant to MCMV; however, infection with Δm04 MCMV abrogates resistance. Depletion of NK cells in MA/My mice abrogates their resistance to wild-type MCMV infection, but does not significantly affect viral titers in mice infected with Δm04 virus, implicating NK cells in host protection through m04-dependent recognition. These findings reveal a novel mechanism of major histocompatability complex class I-restricted recognition of virally infected cells by an activating NK cell receptor.

Original languageEnglish (US)
Pages (from-to)515-523
Number of pages9
JournalJournal of Experimental Medicine
Volume206
Issue number3
DOIs
StatePublished - Mar 16 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Kielczewska, A., Pyzik, M., Sun, T., Krmpotic, A., Lodoen, M. B., Munks, M. W., Babic, M., Hill, A. B., Koszinowski, U. H., Jonjic, S., Lanier, L. L., & Vidal, S. M. (2009). Ly49P recognition of cytomegalovirus-infected cells expressing H2-D k and CMV-encoded m04 correlates with the NK cell antiviral response. Journal of Experimental Medicine, 206(3), 515-523. https://doi.org/10.1084/jem.20080954