Why does the body deem some foods safe and others unsafe?

Amazing stuff!

"Highlights

• Scientists identify three new proteins, one each from soybean, corn, and wheat, that the body uses to determine oral tolerance—the opposite of food allergy
• They found that specialized immune cells called regulatory T cells interact with these proteins in the gut
• By understanding tolerance, researchers can better understand food allergies and begin to imagine future immunotherapies that promote tolerance rather than allergic reactions

...

identifies new bits of food proteins that tell gut immune cells when to tolerate certain foods. They found three of these protein segments, called epitopes—one each from soybean, corn, and wheat. These epitopes interact with specialized immune cells called regulatory T cells to inform that tolerance-or-rejection decision. ..."

"Editor’s summary

Immunological tolerance to dietary antigens is essential for preventing food allergies and digestive disorders such as celiac disease. However, the specific food-derived antigens that contribute to immune tolerance remain poorly described. Blum et al. mapped the dietary epitopes recognized by food-responsive T cell receptors (TCRs) derived from murine intestinal regulatory T (Treg) cells.

Seed storage proteins from corn, wheat, and soy, including the maize protein αZein, were targets of food-responsive Treg cell TCRs. αZein-specific Treg cells suppressed T cell responses to αZein ex vivo and after adoptive transfer into naive mice. These findings provide insight into the dietary components recognized by naturally occurring Treg cells that mediate oral tolerance. ...

Abstract

Food antigens elicit immune tolerance through the action of intestinal regulatory T (Treg) cells. Unlike food allergens, the proteins that mediate tolerance are mostly undescribed.

Here, we found that epitopes derived from seed storage proteins are targets of murine intestinal Treg cells, with the most frequent response targeting the C terminus of the maize protein alpha-zein.

A major histocompatibility complex (MHC) tetramer loaded with this antigen revealed that zein-specific T cells are predominantly intestinal Treg cells, develop concurrently with weaning, and constitute up to 2% of the peripheral Treg cell pool. Zein-responsive Treg cells repressed naïve T cell proliferation ex vivo, and prior dietary exposure resulted in a constrained response upon diverse inflammatory challenges in vivo, supporting a specific role for gut-resident Treg cells in suppressing systemic immune responses.

Our work reveals the development, immune-suppressive characteristics, and function of naturally occurring Treg cells that recognize dietary seed storage proteins, a previously undescribed class of antigens in oral tolerance."

Why does the body deem some foods safe and others unsafe? - Salk Institute for Biological Studies "Study co-led by scientist now at Salk Institute finds three new proteins that the body uses to determine “safe” foods, helping understand food tolerance and allergy"

Identification and characterization of dietary antigens in oral tolerance (no public access)