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FRIBIO-Biologi og biomedisin

The role of T cell specific adapter protein in T cell activation and autoimmunity

Tildelt: kr 3,1 mill.

Genetic variation in genes controlling T cell activation may be responsible for individual differences in fine-tuning of the immune response. Such variability may account for part of the genetic susceptibility to develop autoimmune diseases. Having a majo r interest in elucidating the aetiology of autoimmune diseases, the project group seeks to characterize signalling events in T cells, in particular the role of T cell specific adapter protein (TSAd) encoded by the SH2D2A gene, which our group has cloned a nd partially characterized. Polymorphism in the promoter of the SH2D2A gene may influence the susceptibility to develop multiple sclerosis (MS) and juvenile rheumatoid arthritis (JRA). We have previously shown that TSAd inhibits early T cell signalling events by inhibition of the Src family kinase Lck. TSAd is also expressed in developing endothelial cells and was recently found to modulate tumour vessel formation through interaction with vascular growth factor receptor 2 (VEGFR-2). Our recent data poin ts to a role for TSAd in controlling actin polymerization in and migration of T cells. In this project, we will examine the role of TSAd in T cell activation as well as in development of autoimmune disease, using transgenic mice and a spectrum of immunolo gical and molecular biological methods. The research effort will yield information which may aid the design of therapeutics that could dampen the disease inducing T cells in autoimmune diseases.

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FRIBIO-Biologi og biomedisin

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