How Human NK Cells Respond to MHC Class I Protein Levels
Author Information
Author(s): Almeida Catarina R., Ashkenazi Amit, Shahaf Gitit, Kaplan Deborah, Davis Daniel M., Mehr Ramit
Primary Institution: Imperial College London, London, United Kingdom
Hypothesis
How is the activation and inhibition of human NK cells regulated by the expression level of MHC class I protein on target cells?
Conclusion
Human NK cells differ in their activation thresholds based on the expression of KIR2DL1, which determines the amount of target HLA-Cw6 required for inhibition.
Supporting Evidence
- Different NK cell clones require varying amounts of MHC class I protein for inhibition.
- KIR2DL1 expression is crucial for determining the inhibition threshold of NK cells.
- Mathematical models suggest that NK cell activation may require prior priming.
- Degranulation and IFN-γ secretion are not always correlated in NK cell responses.
Takeaway
This study shows that different human NK cells need different amounts of a protein on target cells to stop working, and this is mostly controlled by a specific receptor called KIR2DL1.
Methodology
The study used target cell transfectants expressing different levels of MHC class I protein and analyzed NK cell responses through degranulation and IFN-γ secretion assays.
Limitations
The study's findings may not fully account for the effects of other receptors on NK cell inhibition thresholds.
Participant Demographics
The study involved primary human NK cell clones from anonymous donors.
Statistical Information
P-Value
p<0.005
Statistical Significance
p<0.005
Digital Object Identifier (DOI)
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