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A truncated human NKG2D splice isoform negatively regulates NKG2D-mediated function
Mobin A Karimi1,2, Oscar Aguilar3, Baixiang Zou1
1Department of Veterinary & Animal Sciences/Immunology, University of Massachusetts, Amherst, MA.
Journal of Immunology (Baltimore, Md. : 1950)
|August 6, 2014
Summary
A new truncated NKG2D receptor variant (NKG2D(TR)) negatively regulates immune cell function. It interferes with the full-length NKG2D receptor (NKG2D(FL)) and its signaling complex, impacting NK and T cell responses.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Natural killer group 2, member D (NKG2D) is a key stimulatory receptor on NK and T cells.
- NKG2D plays a vital role in innate and adaptive immunity.
Purpose of the Study:
- To characterize a novel truncated splice variant of human NKG2D (NKG2D(TR)).
- To investigate the regulatory role of NKG2D(TR) in NKG2D-mediated immune functions.
Main Methods:
- Detection of NKG2D(TR) in primary human NK and CD8(+) T cells.
- Overexpression and knockdown studies of NKG2D(TR).
- Biochemical assays to analyze protein interactions (NKG2D(TR), NKG2D(FL), DAP10).
Main Results:
- NKG2D(TR) was detected in human NK and CD8(+) T cells.
- Overexpression of NKG2D(TR) reduced NKG2D(FL)-mediated cytotoxicity and IFN-γ release.
- Knockdown of NKG2D(TR) enhanced NKG2D-mediated cytotoxicity.
- NKG2D(TR) binds DAP10, interfering with NKG2D(FL)/DAP10 interaction and causing retention of NKG2D(FL).
Conclusions:
- NKG2D(TR) acts as a negative regulator of NKG2D(FL) function.
- Competitive interference with NKG2D/DAP10 complexes by NKG2D(TR) is a novel regulatory mechanism.
- This mechanism impacts human CD8(+) T cell and NK cell functions.
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