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Shifting forms: Penn study shows how variations of same protein affect immune response
Date:10/15/2010

PHILADELPHIA How a T cell decides to make protein X, Y, or Z can have profound effects for fighting foreign invaders or staving off dire autoimmune reactions. Researchers at the University of Pennsylvania School of Medicine have identified the steps that control how different forms of an immune cell protein called CD45, which is critical for activating the immune system when faced with pathogens, are controlled in the arc of a body's immune response.

The shift between different forms of CD45 helps T cells function properly and also prevents hyperactivity, which could lead to the body's own immune system attacking itself. Knowing precisely how this shifting system works has implications for understanding autoimmune and neurological diseases.

"We have identified a new paradigm for the regulation of a process called alternative splicing, which allows for a single gene to code for multiple variations of one type of protein," says Kristen W. Lynch, PhD, associate professor of Biochemistry and Biophysics. This study appeared in an October issue of Molecular Cell.

CD45, a receptor protein that sits on the surface of T cells, is essential for immunity, for example, severe combined immune deficiency (SCID), also known as "bubble boy" syndrome, is caused by the absence of CD45.

Normal CD45 comes in five forms, all different lengths. In resting T cells, longer forms of CD45 messenger RNA (mRNA) and protein predominate, but in activated cells, the shorter form of CD45 mRNA is most abundant. "There is a spectrum of forms that shift toward full length in resting cells and towards the shorter form in activated cells," says Lynch. Messenger RNA contains the chemical blueprint for how to make a protein.

"We knew that a protein called PSF was required for splicing out parts of CD45 RNA to make the different forms," says Lynch. Lynch and post-doctoral fellow Florian Heyd, PhD have shown that there are additional critical compone
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

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