A dual function of NKG2D ligands in NK-cell activation

Elizabeth E. Cheney, Erica L. Wise, Jack D. Bui, Robert D. Schreiber, Leonidas N. Carayannopoulos, Dirk Spitzer, Biljana Zafirova, Bojan Polic, Andrey S. Shaw, Mary A. Markiewicz

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


NK-cell killing requires both the expression of activating receptor ligands and low MHC class I expression by target cells. Here we demonstrate that the expression of any of the murine ligands for the NK-cell activating receptor NKG2D results in a concomitant reduction in MHC class I expression. We show this both in tumor cell lines and in vivo. NK-cell lysis is enhanced by the decrease in MHC class I expression, suggesting the change is biologically relevant. These results demonstrate that NKG2D ligand expression on target cells not only allows for activating receptor recognition, but also actively reduces expression of the inhibitory ligand, MHC class I, leading to enhanced recognition and killing by NK cells.

Original languageEnglish
Pages (from-to)2452-2458
Number of pages7
JournalEuropean Journal of Immunology
Issue number9
StatePublished - Sep 2012


  • MHC class I
  • NK cells
  • NKG2D ligands


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