Closely related proteins less likely to cause allergy

The evolutionary distance between an animal protein and its human equivalent determines whether or not it is likely to cause allergy, a team of British and Austrian scientists has found; the
study reveals that proteins which are closely related to their human homologue are less likely to trigger an allergy than more distantly related proteins.

The work, which was partly funded by the EU, is published by the Journal of Allergy and Clinical Immunology. The researchers hope their findings will make it easier to identify new allergens
and determine how they trigger an immune response.

‘Overall we found that only an animal food protein that is less than 54% identical to a human equivalent could become allergenic,’ said Dr Clare Mills of the Institute of Food Research in
Norwich, UK. ‘This explains why people who are allergic to cow’s milk can often tolerate mare’s milk but not goat’s milk. Proteins in horse milk are up to 66% identical to human milk proteins,
while known allergens from cows and goats are all less than 53% identical to corresponding human proteins.’

The scientists compared the sequences of animal food proteins that are known to cause allergies and found that most of them can be classified into one of three protein families. Tropomyosins,
which are found in muscle tissue, make up the most important family.

‘Tropomyosins in mammals, fish and birds are at least 90% identical to at least one human tropomyosin and none have been reported to be allergenic,’ said Dr Heimo Breiteneder of the Medical
University of Vienna. ‘In contrast, the allergenic tropomyosins are all from invertebrates such as insects, crustaceans and nematodes and at most are only 55% identical to the closest human
homologue.’

The second major allergen family consists of EF-hand proteins. EF-hand proteins found in birds and mammals are not allergenic, while those in frogs and fish can cause allergies. Caseins, which
are all mammalian proteins found in milk, make up the third group identified by the scientists.

‘These data support the premise that certain protein structures are more allergenic than others,’ the scientists write. ‘Contrasting with plant food allergens, animal allergens, such as the
highly conserved tropomyosins, challenge the capability of the human immune system to discriminate between foreign and self proteins.’

‘Immune responses to some animal food allergens, such as the invertebrate tropomyosins, run close to becoming a form of autoimmune response and this needs to be considered when developing
allergy therapies,’ commented Dr Mills.

EU funding for the work came from the Fifth Framework Programme (FP5) project InformAll, which dealt with communicating about food allergies.