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Biological Chemistry

Immune response hinges on pH

July 24, 2006 | A version of this story appeared in Volume 84, Issue 30

New research shows acid neutralization is at the base of the immune system's forensic work. During the immune response, surveillance cells engulf dying cells that are infected by pathogens. Proteins from the devoured cells are chopped up by enzymes and then the fragments, or antigens, are "presented" to T cells so that they can identify and kill invaders. But researchers have long wondered how the antigen proteolysis is controlled in antigen-presenting cells: If antigens are cut too short, there is not enough information to uniquely identify invaders. Too long is information overload. Now, researchers in Sebastian Amigorena's lab at the Curie Institute in Paris have figured out the answer (Cell 2006, 126, 205). It turns out that an oxidase enzyme called NOX2 mediates the production of low levels of reactive oxygen species, causing an alkalinization of the normally acidic compartments where antigen proteolysis takes place. This curbs the enthusiasm of antigen-chopping enzymes, which operate optimally in acidic environments.

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