Key Asthma And Allergy Molecule Pictured

In a finding that is expected to lead to the development of a new class of drugs for allergy and asthma sufferers, researchers at Northwestern University and Harvard Medical School have determined the precise shape of the receptor molecule that triggers the allergic response in the immune system.

The finding, reported in the Dec. 23 issue of the journal Cell, is the first structure reported for a member of this family of antibody receptor proteins. It was made by probing crystals of the receptor called the high-affinity immunoglobulin-E receptor with the extremely brilliant X-rays produced by the Advanced Photon Source synchrotron at Argonne National Laboratory in Illinois.

"We think this identifies the structure that all of the members of this antibody receptor family will have," says Theodore S. Jardetzky, the Northwestern X-ray crystallographer who led the study.

As a class, antibody receptors allow immune system cells to affix antibodies onto the cells' surface to act as antennas for antigens, or foreign triggering substances. When so triggered, the cells respond by unleashing a barrage of immune responses. In the case of allergy and asthma, the high-affinity immunoglobulin-E receptor on the surface of mast cells anchors immunoglobulin-E, an antibody that receives allergens and triggers the mast cells to produce histamine, leukotrienes and other broadly-acting effector substances that lead to the itching, sneezing and congestion of allergies -- and the life-threatening respiratory distress of asthma and anaphylactic shock.

Other members of the antibody receptor family are involved in tumor recognition, autoimmune diseases such as arthritis, and in normal immunity.

The IG-E receptor was of particular interest because an estimated 20 percent of the population suffers from allergies. Asthma afflicts 15 million people in the U.S. and causes 500,000 hospitalizations and 5,000 deaths each year. The National Institutes of Health estimate that di

Contact: Bill Burton
Northwestern University

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