Processing of MHC class II in dendritic cells
The body’s defence against pathogens consists of many links, one of the most important of which is the dendritic cell (DC). Doctoral Candidate Toine ten Broeke has studied the function of DCs, and the results of his research have increased our understanding of the immune system’s defences against pathogens and will contribute to the development of new vaccine strategies.
DCs can recognise proteins in pathogens, ‘consume’ them and break them down into smaller pieces called antigens. The DC then binds the antigens to a special molecule called the major histocompatibility complex (MHC) class II. The DC can then ‘display’ this antigen MHC class II on its cell membrane, allowing it to warn the T cells (immune cells) that the body is under attack. Only those T cells that can recognise the specific pathogen are activated. In his dissertation, Toine ten Broeke examined how DCs regulate the presence of MHC class II on the cell membrane.
The Doctoral Candidate has shown that the presence of MHC II on the cell membrane is primarily determined by regulating the breakdown of the protein. This is controlled by coupling or decoupling ubiquitin molecules, which are the signal for the breakdown of MHC class II. Ten Broeke has also shown that from the moment that the DC absorbs an intruder, newly formed MHC class II molecules are responsible for presenting antigens on the cell membrane. Newly formed MHC class II molecules bind first to the invariant chain (Ii), which is a protein that guides the MHC class II to the location in the cell where the proteins from the pathogen are broken down into antigens. Here, the Ii is also broken down, allowing the MHC class II to bind to antigens. The breakdown of Ii is therefore necessary to the function of MHC class II.
In his dissertation, ten Broeke discusses how the use of glutamine in the cell culture medium inhibits the breakdown of Ii. In contrast to previous assumptions, the breakdown of Ii appears not to be regulated in the DC when the cells are grown in the absence of glutamine. These conclusions have resulted in the development of a method for manipulating the presence of MHC class II on the cell membrane and therefore the warnings transmitted to the T cells.
|Date and time:
||University Hall, Domplein 29, Utrecht
||Toine ten Broeke
||Faculty of Veterinary Medicine
||Processing of MHC class II in dendritic cells
||Prof. Willem Stoorvogel, PhD
||Dr. Richard Wubbolts