The general goal of this project addresses the role the mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R, CD222) in the regulation of T cell activation.
The hypothesis that this receptor is involved in T cell activation has developed through a number of discoveries obtained during our previous FWF project where we have characterized successfully how the M6P/IGF2R negatively controls cell migration of cancer and endothelial cells.
In the course of this project we have started to analyze also T cells and have found that the M6P/IGF2R expression is highly upregulated on the T cell surface upon activation. Further, we have discovered that M6P/IGF2R silencing by RNA interference leads to an altered CD3 surface expression and block of production of the T cell growth factor interleukin-2. In the course of the project we will study in detail the molecular mechanisms underlying the involvements of the M6P/IGF2R and their functional consequences. Basically, we will perform loss-of-function and gain-of-function experiments combined with immunobiochemical and cellular-functional assays as well as with mass spectrometry and ultrasensitive imaging methods.
We are confident that our project will provide a deeper understanding of the molecular pathways and protein interactions involved in T cell signaling; the comprehensive knowledge of these mechanisms is prerequisite to develop specific therapeutic strategies to modulate unwanted immune responses occurring in allergy, autoimmunity, chronic inflammation or post-transplantation complications.
15.07.2010
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