Cutting edge: NK cell licensing modulates adhesion to target cells.
L Michael Thomas1, Mary E Peterson, Eric O Long
1Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852.
Journal of Immunology (Baltimore, Md. : 1950)
|September 17, 2013
Summary
NK cell licensing, a process involving inhibitory receptors and MHC class I, enhances NK cell responsiveness. Unlicensed NK cells show reduced target cell conjugation due to impaired signaling, not integrin function.
Area of Science:
- Immunology
- Cellular Biology
Background:
- NK cell licensing, mediated by inhibitory receptors binding MHC class I, enhances NK cell responsiveness.
- Reduced MHC class I expression or lack of inhibitory receptors diminishes NK cell responsiveness.
Purpose of the Study:
- To investigate the impact of NK cell licensing on early natural cytotoxicity stages in humans and mice.
- To determine the mechanisms behind reduced NK cell conjugation in unlicensed cells.
Main Methods:
- Evaluation of human and mouse NK cell licensing.
- Assessment of NK cell conjugation with target cells.
- Analysis of β2 integrin LFA-1 properties and inside-out signaling.
- Examination of LFA-1-dependent granule polarization.
Main Results:
- Unlicensed NK cells formed fewer stable conjugates with target cells compared to licensed NK cells.
- The reduced conjugation was linked to impaired inside-out signaling to LFA-1 by activating receptors, not altered LFA-1 properties.
- For conjugates that did form, LFA-1-dependent granule polarization was comparable between licensed and unlicensed NK cells.
Conclusions:
- NK cell licensing regulates signaling as early as inside-out signaling initiated by activating receptors.
- Licensing does not affect integrin outside-in signaling crucial for granule polarization.
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