Major histocompatibility class II molecules (MHC class II) are one of the key regulators of adaptive immunity because of their specific expression by professional antigen presenting cells (APC).... Show moreMajor histocompatibility class II molecules (MHC class II) are one of the key regulators of adaptive immunity because of their specific expression by professional antigen presenting cells (APC). They present peptides derived from endocytosed material to T helper lymphocytes. Consequently, MHC class II is fundamental in orchestrating both cellular and humoral immune responses. A genetic association of certain MHC class II alleles with autoimmunity has long been established. The molecular mechanisms underlying this association are only poorly understood. An in depth understanding of the antigen presentation pathway by MHC class II is essential for the improvement of current therapies. In this thesis, the tools to arrive at a systems understanding of MHC class II antigen presentation are discussed. What are the advantages and disadvantages of a genome-wide screen? And how can a multi-dimensional, data-integrating approach increase the understanding of the systems biology of MHC class II? Show less
This thesis centers on the mechanisms of estrogen action and the effects on the development of atherosclerosis. We have focused on the liver as central organ in lipid and glucose metabolism and the... Show moreThis thesis centers on the mechanisms of estrogen action and the effects on the development of atherosclerosis. We have focused on the liver as central organ in lipid and glucose metabolism and the vessel wall as the actual site where the injury occurs. To gain insight in tissue-specific actions of estrogens, we have spent considerable effort to develop tools for liver and blood vessel specific modulation of the estrogen receptor (ER) signaling cascade. The generation, characterization and application of these tools in vitro and in vivo will be described in the different chapters of this thesis. Show less