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Immune Cell Receptors Act In Combination To Regulate Attack

Date:
December 4, 2005
Source:
Rockefeller University
Summary:
Antibodies are one of our best weapons against disease, but some types of antibodies are more effective against pathogens than others. New research by Jeffrey Ravetch at Rockefeller University shows that it is how an antibody interacts with the cells of the immune system that determines how efficiently our bodies deal with infection. The data will help researchers improve on antibody-based cancer therapies.
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FULL STORY

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 receptor, named FcγIV, allows the most efficient IgG isotypes to activate immune cells so they can attack tumor cells, viruses, and other invaders.

“This is very important if you think about antibodies in human therapy,” says Nimmerjahn. Humans and mice have a very similar immune system, “so choosing an antibody with the highest affinity for activating the right combination of Fcγ receptors is critical if you want to improve antibody-mediated cancer therapy, viral therapy, and whatever else you can think of.” Nimmerjahn and Ravetch are now working to create mutant antibodies with an even higher affinity for Fcg receptors, and even more efficient at eliminating tumors.

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Citation: Science 310(5753): 1510-1512 (December 2, 2005)


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Materials provided by Rockefeller University. Note: Content may be edited for style and length.


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Rockefeller University. "Immune Cell Receptors Act In Combination To Regulate Attack." ScienceDaily. ScienceDaily, 4 December 2005. <www.sciencedaily.com/releases/2005/12/051203121955.htm>.
Rockefeller University. (2005, December 4). Immune Cell Receptors Act In Combination To Regulate Attack. ScienceDaily. Retrieved March 29, 2024 from www.sciencedaily.com/releases/2005/12/051203121955.htm
Rockefeller University. "Immune Cell Receptors Act In Combination To Regulate Attack." ScienceDaily. www.sciencedaily.com/releases/2005/12/051203121955.htm (accessed March 29, 2024).

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