Journal
BIOPHYSICAL JOURNAL
Volume 99, Issue 7, Pages 2028-2037Publisher
CELL PRESS
DOI: 10.1016/j.bpj.2010.07.061
Keywords
-
Categories
Funding
- Research Institute at the Nationwide Children's Hospital
Ask authors/readers for more resources
Natural killer (NK) cells extend important immune resistance in vertebrates by lysing infected and tumor cells. A fine balance between opposing signals generated by a diverse set of stimulatory and inhibitory NK-cell receptors determines the fate of target cells interacting with the NK cells. We have developed a mathematical model involving membrane proximal initial signaling events that provides novel mechanistic insights into how activation of NK cells is modulated by the half-life of receptor-ligand interaction and ligand concentrations. We show that strong stimulatory ligands produce digital activation, whereas weaker stimulatory ligands can mediate inhibition by strengthening the signals generated by inhibitory ligands, as indicated in experiments in knockout mice. We find under certain conditions, counterintuitively, inhibitory receptors can help mediate activation instead of inhibition. Mechanistic insights gained from NK-cell signaling can facilitate understanding of complex signaling responses that occur due to cross talk between dueling signaling pathways in other cell types.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available