engleski

NKG2D LIGAND RAE-1delta ESCAPES MCMV DOWN-MODULATION

Natural killer (NK) cells play an important role in the innate immune response against cytomegalovirus (CMV). The mouse NK cell activating receptor NKG2D interacts with three different cellular ligands: RAE-1α , β , γ , δ and ε a family of proteins, H60 and MULT-1. MCMV encodes several proteins that affect expression of NKG2D ligands. We have shown previously that the MCMV m152, m145 and m155 proteins down modulate the surface expression of RAE-1, MULT1 and H60 proteins, respectively. By doing so the virus prevents activation of NK cells via activating receptor NKG2D. In contrast to original findings, here we show that some NKG2D ligands can escape viral downmodulation. By help of monoclonal antibodies directed against different isoforms of RAE-1 proteins we have demonstrated that RAE-1δ is resistant to down-regulation by MCMV m152– encoded gp40. Furthermore, we have also shown that mice expressing RAE-1α , β , γ are resistant to MCMV in NKG2D-dependent manner, suggesting the in vivo significance of RAE-1δ escape from MCMV immunoevasins.

cytomegalovirus; NK cells; NKG2D; RAE-1

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