Inhibition of the NKp30 activating receptor by pp65 of human cytomegalovirus.
Human cytomegalovirus, a chief pathogen in immunocompromised people, can persist in a healthy immunocompetent host throughout life without being eliminated by the immune system. Here we show that pp65, the main tegument protein of human cytomegalovirus, inhibited natural killer cell cytotoxicity by an interaction with the activating receptor NKp30. This interaction was direct and specific, leading to dissociation of the linked CD3zeta from NKp30 and, consequently, to reduced killing. Thus, pp65 is a ligand for the NKp30 receptor and demonstrates a unique mechanism by which an intracellular viral protein causes general suppression of natural killer cell cytotoxicity by specific interaction w…
Classification of current anticancer immunotherapies.
© 2014. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Mechanical Regulation of the Cytotoxic Activity of Natural Killer Cells
AbstractMechanosensing has been recently explored for T cells and B cells and is believed to be part of their activation mechanism. Here, we explore the mechanosensing of the third type of lymphocytes – Natural Killer (NK) cells, by showing that they modulate their immune activity in response to changes in the stiffness of a stimulating surface. Interestingly, we found that this immune response is bell-shaped, and peaks for a stiffness of a few hundreds of kPa. This bell-shape behavior was observed only for surfaces functionalized with the activating ligand MHC class I polypeptide-related sequence A (MICA), but not for control surfaces lacking immunoactive functionalities. We found that sti…