Expression Analysis of the Ligands for the Natural Killer Cell Receptors NKp30 and NKp44

Abstract

BackgroundThe natural cytotoxicity receptors (NCR) are important to stimulate the activity of Natural Killer (NK) cells against transformed cells. Identification of NCR ligands and their level of expression on normal and neoplastic cells has important implications for the rational design of immunotherapy strategies for cancer.Methodology/Principal FindingsHere we analyze the expression of NKp30 ligand and NKp44 ligand on 30 transformed or non-transformed cell lines of different origin. We find intracellular and surface expression of these two ligands on almost all cell lines tested. Expression of NKp30 and NKp44 ligands was variable and did not correlate with the origin of the cell line. Expression of NKp30 and NKp44 ligand correlated with NKp30 and NKp44-mediated NK cell lysis of tumor cells, respectively. The surface expression of NKp30 ligand and NKp44 ligand was sensitive to trypsin treatment and was reduced in cells arrested in G2/M phase.Conclusion/SignificanceThese data demonstrate the ubiquitous expression of the ligands for NKp30 and NKp44 and give an important insight into the regulation of these ligands.

The proto-oncogene Myc drives expression of the NK cell-activating NKp30 ligand B7-H6 in tumor cells

“…The family of NCRs comprises three members, NKp30, NKp44 and NKp46 all of which are involved in the killing of tumor cells. 4,5 NKp30 belongs to the CD28 family and is expressed on the majority of NK cells. 2 It is not only involved in tumor cell lysis but also in the interaction with dendritic cells.…”

Mimicking an Induced Self Phenotype by Coating Lymphomas with the NKp30 Ligand B7-H6 Promotes NK Cell Cytotoxicity

“…NKp30 promotes independently or together with other stimulatory receptors the recognition and killing of tumor cells by NK cells (8,12). NKp30-specific ligands are expressed on different types of tumors that have been demonstrated to be lysed by NK cells in an NKp30-dependent manner (8,(12)(13)(14)(15). Ligation of NKp30, moreover, has been shown to trigger the release of immunostimulatory cytokines such as TNF-a and IFN-g (16,17).…”

Ex vivo differentiation of natural killer cells from human umbilical cord blood CD34+progenitor cells

“…Although K562 cells do not carry HLA-E, it was proposed by Figueiredo. et al that this increased cytolytic activity is partially mediated by the natural cytotoxicity receptor NKp30 (Figueiredo, Settsam, & Blasczyk, 2009) since it was recently shown that the ligand of NKp30 is expressed in K562 cells (Byrd, Hoffmann, Jarahian, Momburg, & Watzl, 2007). In general, the stroma was a more potent inducer for cord blood differentiation into functional NK cells than the other experimental conditions.…”