Manipulating Pollen Allergen Genes for Improved Diagnosis and Immunotherapy of Hayfever and Allergic Asthma
A substantial proportion (2025%) of the human population living in temperate and subtropical climates suffers from allergic rhinitis and seasonal asthma. Grass pollen allergy is one of the most common allergies worldwide and airborne allergens from grass pollen are the major elicitors of type 1 allergic reactions such as hayfever and seasonal asthma. To date, eleven groups of allergens have been reported in pollens from common grasses (Pooideae species). Groups 1 and 5 allergens are the most critical (major) pollen allergens leading to the sensitization of 95% and 70–90% allergic patients, respectively.
We are the first in the world to identify and clone major pollen allergen genes of ryegrass and rice. In order to obtain a comprehensive understanding of allergen encoding potential of grass pollen allergens we used microarray and RNA-seq approach to map mature pollen transcriptome of rice (Oryza sativa ssp japonica), ryegrass (Lolium perenne; subfamily Pooideae) and Bermuda grass (Cynodon dactylon; subfamily Chloridoideae). Our research has provided valuable allergen gene repertoire data for further investigations of the molecular basis of allergenicity and for designing effective specific immunotherapy reagents. Further, in order to understand structural basis of IgE reactivity of grass group 1 allergens, we are following a comparative genomic approach to search for hypoallergenic or non-allergenic homologues. EXPB1, an Arabidopsis protein (belonging to the beta expansin multi gene family), showed significant sequence and structural similarity to Cyn d 1. This protein was expressed in E. coli and the recombinant protein did not react with serum IgE from grass pollen allergic patients, suggesting that EXPB1 represented a non-allergenic homologue of grass group 1 allergens. Currently we are exploring use of this non-allergenic member of group 1 family for revealing molecular basis of allergenicity with an aim to generate hypo-allergenic forms of grass group 1 allergens suitable as immunotherapy vaccines.