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Immune cell receptors act in combination to regulate attack

The complexities of the mammalian immune system allow our bodies to fend off countless diseases. But researchers are still working to pin down exactly how it works -- and to understand why some people's antibodies, and some therapeutic antibodies, are better able to fight off disease than others'. In research published in today's issue of Science, Rockefeller researchers show how a newly discovered receptor may be partly responsible.

Two competing theories exist as to why some subclasses of antibodies, called IgG isotypes, are more effective against pathogens than others. The older and most-accepted model holds that certain isotypes are better at activating blood proteins called complement, which bind to a viral, bacterial or tumor cell and kill it by punching holes in its surface. An alternative model, however, suggests that the different isotypes have varying affinities to the four different antibody receptors on an immune cell's surface -- three of these receptors act as activators, one acts as an inhibitor, and together they determine whether the cell is turned on or off.

A new study by Jeffrey Ravetch, head of Rockefeller's Leonard Wagner Laboratory of Molecular Genetics and Immunology, and Falk Nimmerjahn, a postdoctoral fellow in the lab and the paper's first author, provides overwhelming evidence in favor of the second theory. Their research shows that it's the receptors that dictate how efficiently an antibody will recognize a foreign cell, bind to it, and destroy it. By studying mice in which one receptor at a time was blocked, and then comparing their ability to fight off tumors, Ravetch and Nimmerjahn illustrate how a receptor they'd discovered earlier this year is a vital piece of the puzzle. It seems that different antibody isotypes bind to different receptors, thus determining how effectively a foreign cell will be destroyed: If the antibody selectively engages only the inhibitory receptor, the immune cell won't attack. The new recepto
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Contact: Kristine Kelly
kkelly@rockefeller.edu
212-327-7146
Rockefeller University
2-Dec-2005


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