What makes an allergen an allergen?

An enduring mystery for allergy researchers has been the unpredictable distribution of allergens in plants. For example, being allergic to birch pollen can predispose a person to allergy from distantly related plant foods such as celery, apple or soy.

Most allergens are proteins. Research published on Tuesday identifies 129 plant allergens in just four main protein families.

“Knowing what makes a protein more likely to become an allergen could make it easier for manufacturers to identify potential allergens in novel foods and ingredients, preventing them from reaching the consumer”, said Dr Clare Mills, head of the allergy research team at the UK’s Institute of Food Research.

Proteins are constructed from amino acids, and previous research has focused on analysing the sequence of amino acids to identify potential allergens. However, this can lead to false predictions. Sequence data alone does not reveal how amino acids interact to construct proteins.

The interaction of amino acids creates proteins folded into particular shapes. The new research by a team of scientists considered both amino acid sequence and structural similarities between surface features of plant proteins using a 3D computer model.

“By modelling surface features of proteins from a range of flowering plants, we were able to explain why cross-reactions can occur between species that otherwise seem dissimilar”, said Dr Mills. “This is especially important to help us understand why people with allergy to birch pollen can suffer related allergies to fresh fruits and vegetables”.

Flowering plants first appeared over 100 million years ago during the late Jurassic period, the age of the dinosaurs. Flowering plants became the most dominant plant on Earth and today include all our food plants. Very early in their evolution there was a split into two major groups. Some plant protein structures changed and some stayed the same or were ‘conserved’.

“We found that even a single conserved region on the surface structure of a protein can cause cross-reactivity”, said Dr Heimo Breiteneder of the Medical University of Vienna.

Scientists had already observed that although humans consume an enormous diversity of plant foods, just a few foods account for the majority of food allergies. However, their relatedness remained unclear. For the first time, the distribution of plant food allergens has been measured according to protein families. The scientists found that 129 allergens could be classified into just 20 out of 3849 possible protein families, with just four ‘superfamilies’ accounting for more than 65% of food allergens.

“We are only now in a position to begin to understand what makes an allergen an allergen”, said Dr Breiteneder.

The research, published in the Journal of Allergy and Clinical Immunology, was funded through the Biotechnology and Biological Sciences Research Council (BBSRC) competitive strategic grant to IFR and Rothamsted Research with additional support from the EU. The research is featured as “The Editor’s Choice” in the journal. Breitenender and Mills have published a review of the molecular properties of food allergens in the same issue.