The nkg2d ligands rae-1dδ and rae-1eε differ with respect to their receptor affinity, expression profiles and transcriptional regulation

Abstract

Background: RAE-1 is a ligand of the activating receptor NKG2D expressed by NK cells, NKT, cdT and some CD8+T lymphocytes. RAE-1 is over expressed in tumor cell lines and its expression is induced after viral infection and genotoxic stress. We have recently demonstrated that RAE-1 is expressed in the adult subventricular zone (SVZ) from C57BL/6 mice. RAE-1 is also expressed in vitro by neural stem/progenitor cells (NSPCs) and plays a non-immune role in cell proliferation. The C57BL/6 mouse genome contains two rae-1 genes, rae-1dδ and rae-1eε encoding two different proteins. The goals of this study are first to characterize the in vivo and in vitro expression of each gene and secondly to elucidate the mechanisms underlying their respective expression, which are far from known. Principal Findings: We observed that Rae-1dδ and Rae-1eε transcripts are differentially expressed according to tissues, pathological conditions and cell lines. Embryonic tissue and the adult SVZ mainly expressed Rae-1dδ transcripts. The NSPCs derived from the SVZ also mainly expressed RAE-1dδ. The interest of this result is especially related to the observation that RAE-1dδ is a weak NKG2D ligand compared to RAE-1eε. On the contrary, cell lines expressed either similar levels of RAE-1dδ and RAE-1eε proteins or only RAE-1eε Since the protein expression correlated with the level of transcripts for each rae-1 gene, we postulated that transcriptional regulation is one of the main processes explaining the difference between RAE-1dδ and RAE-1eε expression. We indeed identified two different promoter regions for each gene: one mainly involved in the control of rae- 1dδ gene expression and the other in the control of rae-1eε expression. Conclusions/Significance: RAE-1dδ and RAE-1eε differ with respect to their function and the control of their expression. Immune function would be mainly exerted by RAE-1eε and non-immune function by RAE-1dδ. © 2010 Cédile et al.