Spatially resolved in silico modeling of NKG2D signaling kinetics suggests a key role of NKG2D and Vav1 Co-clustering in generating natural killer cell activation.

ABSTRACT: Natural Killer (NK) cells provide key resistance against viral infections and tumors. A diverse set of activating and inhibitory NK cell receptors (NKRs) interact with cognate ligands presented by target host cells, where integration of dueling signals initiated by the ligand-NKR interactions determines NK cell activation or tolerance. Imaging experiments over decades have shown micron and sub-micron scale spatial clustering of activating and inhibitory NKRs. The mechanistic roles of these clusters in affecting downstream signaling and activation are often unclear. To this end, we developed a predictive in silico framework by combining spatially resolved mechanistic agent based modeling, published TIRF imaging data, and parameter estimation to determine mechanisms by which formation and sp

SUBMITTER: Grewal RK 

PROVIDER: S-EPMC9154193 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature