T-CELLESPESIFIKT ADAPTERPROTEIN (TSAd) : Fra oppdagelsen av et protein til muligheten for klinisk intervensjon

Abstract

The SH2D2A gene codes for a protein which was named T cell specific adapter protein (TSAd) by the group who cloned it in 1997. The gene is located to 1q21, a region where several immunoregulative genes are situated. The protein includes an SH2 domain, an SH3 ligand, PTB ligands and several tyrosines and serine/threonin phosphorylation sites. TSAd is mainly expressed in hematopoietic and epithelial cell lines, especially T cells, and are induced after stimulation of these cells.

The function of TSAd is still unknown, but it is believed to be involved in regulation of signal transduction and transportation of protein in many signaling systems and celltypes. It is shown that TSAd interact with many proteins and receptors, which may regulate cell proliferation, differentiation and apoptose, including angiogenesis and organization of epithelial tissue. TSAd may also function as a transcription factor.

TSAd -/- knock out mice develops an autoimmune lupus like disease, and short allel variants of the SH2D2A gene are associated with multiple sclerosis and juvenile rheumatoid arthritis.

In my own research, where I mainly use immunohistochemistry in vivo, I show that anti TSAd antibodies stain many tissues collected from both normal, immunostimulated and knock out mice. However, no significant differences are seen. This means that some of the staining is not specific, and no major conclusions can be drawn from the results. Furthermore, affinity purification of the antibodies does not improve the results in vivo, although a minor improvement may be seen on Western blot.