Glycosylation is the modification of macromolecules with carbohydrate structures. These carbohydrate structures together make up a layer at the outside of all of our cells, which we call the glycocalyx or the cell surface glycome. Recently, technology has become available to very specifically introduce genetic modifications in mammalian cells. In this project, we want to further develop this technology to introduce specific changes in the cell surface glycome of cytotoxic Tcells (CTLs). There are strong indications that such glycome-manipulations could have a strong impact on the functionality of these cells, a.o. as CTLs with changed glycotypes could become less sensitive to certain activity-suppressing lectin signals that are produced by tumors and other inflamed tissues. The project encompasses the design and implementation of a novel antigen recognition-inducible gene suppression technology, combined with the optimization and use of flow cytometrical glycan detection assays. The results will greatly expand our fundamental knowledge about the structure-function relationship of the cell surface glycome of these CTL cells, and it is expectable that this knowledge may in the future also have impact on the design of improved CTL-based treatments.