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NKG2D receptor-mediated NK cell function is regulated by inhibitory Ly49 receptors. Blood 2005 Jan 01;105(1):233-40

Date

08/26/2004

Pubmed ID

15328154

Pubmed Central ID

PMC3889208

DOI

10.1182/blood-2004-03-1075

Scopus ID

2-s2.0-11144236862   46 Citations

Abstract

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.

Author List

Regunathan J, Chen Y, Wang D, Malarkannan S

Authors

Subramaniam Malarkannan PhD Professor in the Medicine department at Medical College of Wisconsin
Demin Wang PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Active Transport, Cell Nucleus
Animals
Antibodies, Monoclonal
Antigens, Ly
Cell Nucleus
Cells, Cultured
Cytotoxicity, Immunologic
Down-Regulation
H-2 Antigens
Histocompatibility Antigen H-2D
Humans
Killer Cells, Natural
Lectins, C-Type
Ligands
Mice
Minor Histocompatibility Antigens
NF-kappa B
NK Cell Lectin-Like Receptor Subfamily A
NK Cell Lectin-Like Receptor Subfamily K
Receptors, Immunologic
Receptors, NK Cell Lectin-Like
Receptors, Natural Killer Cell
Signal Transduction
jenkins-FCD Prod-469 c3fc8ab87196149f9b23743c01b947d47e7319e5