Institute AG Wienands
Research topics (AG Dressel)
The Dressel research group deals with the major histocompatibility complex (MHC) and the function of certain MHC-linked genes. Research questions come in particular from the fields of tumour immunology and transplantation immunology. The function and role of cytotoxic cells is in the centre of the interest.
The MHC has a central role in the development of the immune system and in the establishment of an immune response. The so-called class I and class II genes control the antigen-specific adaptive immune response. Certain class I and other genes of the MHC are involved in innate immunity. The rat MHC, the RT1 complex, encodes over 120 functional genes and, in addition, more than 50 members of the class I multigene family. To analyse the expression of these genes, we have established a MHC gene microarray, which is used to determine gene expression in a rat model of graft versus host disease.
Within the MHC three heat shock protein (HSP) 70 genes are encoded that play a role in tumour immunity. In recent years, certain heat shock proteins were shown to participate in antigen presentation and in activation of the innate immune system. We studied the effects of HSP70 overexpression in tumour cells. An increase of natural killer (NK) cell activity mediated by HSP70 released from tumour cells has been observed that was directed against tumour cells expressing ligands for the activating NK receptor NKG2D. Furthermore, the role of polymorphisms in HSP70 receptor genes and NKG2D ligands for the immunological functions of HSP70 is being investigated. In the context of analysing susceptibility of tumour cells to cytotoxic T lymphocytes (CTL), the role of HSP70 and heparan sulfates for granzyme-mediated apoptosis is studied. Several proteins taking part in the transport of intracellular vesicles are analysed in knock-out mice with respect to their role in exocytosis of cytotoxic granules.
The discovery of new pluripotent stem cell types has improved the perspectives of using stem cells for therapeutic purposes. We have started to study the immunogenicity and tumourigenicity of pluripotent stem cells, progenitor cells, and differentiated cells and their susceptibility to immunological cytotoxicity. We could show that in immunosuppressed rats only in vitro differentiated neuronal cells but not undifferentiated embryonic stem cells formed teratomas. It turned out that embryonic stem cells, in contrast to differentiated cells, express NKG2D ligands and are, therefore, efficiently killed by NK cells. These results lead to the question whether the innate immune system can participate in the control of tumorigenicity of pluripotent stem cells.
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