16 Pollen Allergens Differ From Nonallergenic Pollen Proteins by Their Lower Extent of Evolutionary Conservation

BACKGROUND: Pollen contains hundreds of different proteins. However, only a small fraction of them have been identified to be allergenic. We aimed to test the hypothesis that most pollen proteins are non-allergenic due to their high extent of sequence conservation among non-related species. METHODS: Data on the composition of pollen proteomes of birch (Betula pendula), pellitory (Parientaria judaica) and timothy grass (Phleum pratense) were obtained from the literature. Sequences were downloaded from UniProt and manually classified into allergens and non-allergens. Complete proteome sequences of 3 dicotyledonous species (Arabidopsis thaliana, Populus trichocarpa and Vitis vinifera), 2 monocotyledons (Oryza sativa subsp. japonica and Zea mays) and one moss (Physcomitrella patents) were downloaded from ENSEMBL Plants. Sequences of pollen proteins were compared to these proteomes by using BLAST and the hits yielding the highest sequence identity recorded taking into account only sequence alignments at least 40 residues in length. The distributions of maximum sequence identities of allergens and non-allergens from each species were compared using the Mann-Whitney test. RESULTS: Allergens from birch and pellitory pollen were significantly (P < 0.001) less similar to proteins from monocots than non-allergenic pollen proteins. Median sequence identities to the nearest rice and maize homologues were 49 and 52% for birch allergens, 86 and 85% for birch non-allergens, 37 and 37% for pellitory allergens, and 87 and 89% for pellitory non-allergens. Similarly, timothy grass pollen allergens were significantly (P < 0.0001) less similar to dicot proteins than non-allergenic pollen proteins. Median sequence identities to the nearest homologues were 43 to 44% for allergens and 81 to 83% for non-allergens. A comparison of all 3 pollen proteomes to sequences from the moss P. patens yielded similarly significant differences. CONCLUSIONS: Pollen allergens belong to evolutionary less conserved protein families than non-allergenic pollen proteins. The continual exposure of the human immune system to nearly identical and hence highly cross-reactive conserved proteins from multiple pollen and plant food species most likely leads to the induction of immunological tolerance rather than allergic sensitization.