Interactions of the dendritic cell: from pathogen to T cell

Dendritic cells (DCs) are a type of white blood cells. They ingest pathogens, migrate to the lymph nodes and subsequently present fragments of the pathogens on their surfaces. T cells can recognize these fragments, and strong binding can activate them. Activated T cells divide, and thereby form a large army that fights against the pathogens. This activation of the adaptive immune system requires the interaction of DCs with pathogens, the extracellular matrix (to enable migration) and T cells.
In this thesis, we zoom in on different aspects of these interactions. We studied the effects of two new inhibitors on the protein LC3, which amongst others, binds to vesicles containing ingested pathogens that can be present in DCs. In addition, we discovered large spiral-shaped protein structures (consisting of ESCRT proteins) at the surface of DCs and other migratory cells. We found that these structures wrapped around clusters of anchors of the cell (integrins). Disruption of the cell skeleton induced an increase in the number of structures, in concert with an increased capacity of the cell to adhere to its environment. These findings suggest that the structures serve to support the cell surface at vulnerable sites (surrounding anchors and/or in the absence of cell skeleton). In the final research chapter we compared two assays for the determination of T cell division. A new method, based on the incorporation of a nucleoside-analog into the DNA, was more sensitive and less damaging than a standard method based on CellTrace.