Structural Studies of the Gammadelta T Cell Receptor Complex

The most essential function of the highly differentiated and adaptive human immune system is the defense of invading microorganisms, foreign or toxic substances, and the suppression of tumors. The two main components of the immune system are the innate and the adaptive immune response. The latter is mediated via B and T lymphocytes, both of which cells bear surface-exposed receptor proteins. Antigen recognition and binding to these receptors results in transmembrane signal transduction processes, which lead either to programmed cell death or to proliferation and differentiation. T cell receptors (TCRs) are a complex assembly of the actual receptor and numerous coreceptors and accessory molecules. The concerted activity of those is responsible for activation, regulation and fine tuning of the signaling complex. The aim of this research proposal is the investigation of the role of the essential CD3 coreceptor within the d TCR signaling complex. The interplay of the proteins, which are expressed in cell cultures, will be monitored using biophysical methods and by determination of three-dimensional structures of the complex by X-ray crystallography. The results of these studies will lead to a more detailed understanding of the d TCR-CD3 interaction on a molecular level. Additionally to the information on the CD3 coreceptor, the data will provide a glimpse on the up to date unknown role and functionality of d T cells in the human immune system.