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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

NKG2D receptor- mediated NK cell function is regulated by inhibitory Ly49 receptors.

Interaction of the activating ligand H60 with NKG2D receptor constitutes a major stimulatory pathway for natural killer (NK) cells. The influence of inhibitory Ly49 receptors on NKG2D-mediated activation is not clearly understood. Here we show that the magnitude of NKG2D- mediated cytotoxicity is directly proportional to both the levels of H60 and the nature of major histocompatibility complex (MHC) class I molecules expressed on the target cells. The expression levels of H60 on the target cells determined the extent to which the inhibition by Ly49C/I receptors can be overridden. In contrast, even a higher expression of H60 molecule on the target cells failed to overcome the inhibition mediated by Ly49A/G receptors. Also, the level of interferon-gamma ( IFN-gamma) and granulocyte-macrophage colony- stimulating factor ( GM-CSF) generated by NK cells through anti-NKG2D monoclonal antibody (mAb)- mediated activation is significantly reduced by the presence of immobilized anti-Ly49A/G mAbs. Thus, NKG2D-mediated cytotoxicity and cytokine secretion results from the fine balance between activating and inhibitory receptors, thereby defining the NK cell-mediated immune responses.[1]


  1. NKG2D receptor-mediated NK cell function is regulated by inhibitory Ly49 receptors. Regunathan, J., Chen, Y., Wang, D., Malarkannan, S. Blood (2005) [Pubmed]
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