The Austrian Science Fund accepts Vladimir Leksa´s project " Regulation of T cell activation by CD222"

At the last board meeting in June 2010, the Austrian Science Fund (FWF) accepted the project "The Integral Regulatory Role of the Mannose-6-Phosphate/Insulin-like Growth Factor 2 Receptor (CD222) in T cell activation" by Vladimir Leksa with a budget of nearly 400,000 Euros.

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