The human immune system is intrinsically programmed to recognize peanut proteins, according to NIEHS scientists and their collaborators. Moreover, the scientists found people across the age spectrum — from infants to adults — produce very similar immune responses, although some responses are better at tamping down the effects of peanut allergens.

Food allergens are specific food proteins that trigger an abnormal immune response in some individuals, leading to an allergic reaction. These reactions can range from mild (e.g., itching, hives) to severe (e.g., breathing difficulties and a drop in blood pressure), with some being potentially life-threatening.

Many healthy people develop food-specific antibodies, which are Y-shaped proteins produced by the body’s immune system to identify and neutralize foreign substances. The antibodies bind to specific food allergens or other antigens that can trigger an immune response.

“We’ve discovered that certain antibodies have a better neutralizing power than others, and that patients from different backgrounds seem to make very similar antibodies,” said study co-author Geoffrey Mueller, Ph.D., director of the Nuclear Magnetic Resonance (NMR) Group and the NIEHS NMR Research Core Facility.

He explained that the similarity of the antibodies from genetically unrelated patients — called convergence — was surprising because normally the process of developing antibodies can create a very large number of possibilities. Tools developed at NIEHS helped measure the number of people producing convergent antibodies.

The study was published in the journal Science Translational Medicine, June 11.

People make similar antibodies

Mueller and his collaborator Sarita Patil, M.D., at Massachusetts General Hospital, first began characterizing the antibodies that patients make to peanut allergens to understand why oral immunotherapy to peanuts only sometimes produces lasting tolerance. Immunotherapy is a treatment for peanut allergy that involves gradually increasing a patient’s exposure to peanut protein to build tolerance.

To understand this phenomenon, the researchers investigated the most common of the convergent antibody groups. They traced backward from the mature antibodies to the original germline antibodies first produced by B-cells. These specialized immune cells randomly recombine different bits of DNA to make germline antibodies.

“Much to our surprise, it appears incredibly easy for human B-cells to find genetic rearrangements that make a germline antibody more likely to bind to a peanut protein,” Mueller said.

The researchers found that these genetic rearrangements in B-cells were common among the general population. They also learned that asymptomatic infants made similar antibodies after consuming peanuts.

Data produced at NIEHS was critical for analyzing the likelihood of the germline antibodies to bind to the peanut allergen. It also helped explain how the different germline antibody recombinations bound to the allergen.

Questions for future research

The potential clinical implications of the findings warrant further investigation, and two important questions remain, according to Mueller. First, does this propensity for high-affinity peanut antibodies contribute to the frequent development of peanut allergies? Second, what environmental factors might skew the type of antibody made and, as a result, the immune response?

“Future studies will be essential for understanding the broader implications of convergence to dietary antigen recognition and its role in immunity,” Mueller said.

That will be the next challenge Mueller and his NIEHS co-authors — Guangning Zong, Ph.D., Jungki Min, Ph.D., Isabelle Lytle, and Lars Pedersen, Ph.D. — will tackle.