title: A dual function of NKG2D ligands in NK-cell activation.
abstract: 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.
authors: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors: Elizabeth E
authors: EE
authors: Cheney
authors: Erica L
authors: EL
authors: Wise
authors: Jack D
authors: JD
authors: Bui
authors: Robert D
authors: RD
authors: Schreiber
authors: Leonidas N
authors: LN
authors: Carayannopoulos
authors: Dirk
authors: D
authors: Spitzer
authors: Biljana
authors: B
authors: Zafirova
authors: Bojan
authors: B
authors: Polic
authors: Andrey S
authors: AS
authors: Shaw
authors: Mary A
authors: MA
authors: Markiewicz
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics / Q000276:immunology; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; C527086:Klrk1 protein, mouse; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K; D034521:Nuclear Matrix-Associated Proteins; D029543:Nucleocytoplasmic Transport Proteins; C490521:Rae1 protein, mouse