Why can one person eat peanuts, wheat, or soy without any problem while another person faces a dangerous allergic reaction from the same foods? Scientists have studied allergies for many years, but the answer to this question has remained unclear.
A new study from Stanford University is helping researchers understand how the body learns to safely accept many common foods.
Food allergies affect millions of people worldwide. Some reactions cause mild symptoms like itching or swelling. Others can become life-threatening.
The new research suggests that the immune system actively learns which foods are safe instead of simply ignoring them. Understanding this process could help scientists develop new ways to prevent or treat food allergies.
How the body learns food is safe
Every day, the human body encounters thousands of molecules from food. The immune system must decide whether these molecules are dangerous or harmless.
In most people, the body accepts these foods without any reaction. Scientists call this process oral tolerance.
Elizabeth Sattely, an associate professor of chemical engineering in the School of Engineering at Stanford University, pointed out that scientists once misunderstood this process.
“We know a lot about what the immune system sees and does if a patient has an allergy, but we know very little about what happens when things go right,” said Sattely.
The new research shows that tolerance is not passive. The immune system actively checks the food that enters the body and decides whether it is safe.
Immune system’s peacekeepers
Inside the intestines, special immune cells constantly monitor the food that people eat. These cells are called regulatory T cells, or Tregs. Scientists often describe these cells as peacekeepers of the immune system.
Tregs search for specific proteins in food. When these cells detect certain signals, they calm the immune system and prevent an allergic reaction. This response allows the body to accept food safely.
If the immune system fails to receive the correct signal, another type of immune response may occur. That response can trigger inflammation and allergic symptoms.
The Stanford University research team wanted to understand exactly what signals Tregs are searching for in everyday foods.
Finding the signals in food
The study team included Jamie Blum, a former postdoctoral scholar in Sattely’s lab, Ryan Kong, a Stanford University graduate student in chemical engineering, and Kazuki Nagashima.
The group examined proteins in common foods such as corn, soy, and wheat.
The researchers discovered that Tregs respond strongly to small fragments of proteins. Scientists call these fragments epitopes. These short sequences act like signals that tell the immune system that the food is safe.
Not every protein fragment produces this effect. The immune system reacts strongly only to certain epitopes.
“We found that the regulatory T cells are sort of biased towards some peptides more than others,” Sattely said. “Not all of your food is being seen equally by the immune system. The T cells are looking for these specific proteins.”
This discovery suggests that only a few key molecular signals may guide the body toward food tolerance.
A key signal hidden in corn
One finding surprised the researchers. The immune system sometimes focuses on a single protein fragment within a much larger food molecule.
Ryan Kong studied a protein called zein, which is found inside corn kernels. Among many possible fragments, Tregs strongly responded to just one specific epitope from this protein.
“What really surprised me was how focused the mechanism is. In the case of corn, the Treg cells zero in on a single epitope that is part of a larger molecule, zein, a protein in the fleshy interior of the corn kernel,” Kong noted.
This targeted reaction shows how precise the immune system can be. Even though the intestines contain many different food molecules, the immune system may rely on only a few signals to maintain tolerance.
Food and microbes affect tolerance
The research also revealed another interesting detail. The form of the protein in food matters. The gut microbiome plays an important role as well.
Jamie Blum, who now leads a research group at the Salk Institute for Biological Studies, noted that both factors influence how the immune system learns tolerance.
“One of the most exciting findings is that the development of the zein-specific T cells depends on the format of the protein in the food and the intestinal microbial community,” Blum said.
This means that food structure and gut bacteria together shape how the immune system responds to what people eat.
Future treatments for food allergies
The discovery opens exciting possibilities for future medical treatments. Scientists may be able to create a library of tolerance-linked protein fragments that help train the immune system.
Doctors could use these fragments to guide the immune system toward tolerance instead of allergy. Such treatments might help people who already have food allergies.
Another possibility involves prevention. Early exposure to certain protein signals might help children develop tolerance before allergies appear.
“We might be able to treat a patient who currently has a food allergy and induce these regulatory T cells that would allow them to overcome their allergy,” Sattely said. “Or we could design early-stage childhood exposures that would guide allergy-prone patients toward tolerance before allergies develop.”
Training the body to accept food
Sattely’s future research will explore the chemistry of food proteins, especially those found in seeds that form a major part of human diets. The research team plans to study how changes in these proteins influence immune responses.
Scientists may even create modified versions of plant proteins to test how the immune system reacts. Early studies will continue in mice before researchers move toward human studies.
This research also shows something important about food allergies. Food tolerance does not just happen on its own.
The immune system learns to recognize certain protein signals that tell the body a food is safe. This discovery could help millions of people someday eat without fear of allergic reactions.
The study is published in the journal Science Immunology.
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