Antibody Fc receptor CD16a mediates natural killer cell activation via mechanotransduction of piconewton forces
Ma, R.; Garcia, K. C.; Cui, B.; Covert, M. W.
Show abstract
Natural Killer(NK) cells eliminate target cells through antibody-dependent cell-mediated cytotoxicity(ADCC), initiated by CD16a(Fc{gamma}RIIIa) recognizing the Fc region of antibodies bound to the target cell surface. While the recognition is considered to be driven by CD16a-Fc binding avidity, it fails to explain why Fc multimers inhibit ADCC rather than trigger it. Here, we reveal that CD16a transduces piconewton forces, and acts as a mechanosensor to facilitate NK activation. We demonstrate that CD16a force and the actin foci formation associated with it are essential for the phosphorylation of mechanosensitive adaptor Cas-L and signaling adaptor LAT, reshaping NK cell cytoskeletal dynamics and signaling. Our findings show that NK activation is an intricate process that integrates both biochemical and biophysical information, and provides new mechanistic insight for immunoengineering.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Differential Roles of Kinetic On- and Off-Rates in T-Cell Receptor Signal Integration Revealed with a Modified Fab'-DNA Ligand 95%
- Antigen mobility regulates the dynamics and precision of antigen capture in the B cell immune synapse 95%
- The Spread of Interferon-γ in Melanomas is Highly Spatially Confined, Driving Non-Genetic Variability in Tumor Cells 94%
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.