Molecular variability of group 1 and 5 grass pollen allergens between Pooideae species: implications for immunotherapy

P>Background Differences between major allergens from distinct grass species remain to be investigated, both in terms of structure and antigenicity. Methods Group 1 and 5 allergens purified from five common Pooideae species were analysed by mass spectrometry (MS). Major histocompatibility complex (MHC) class II-restricted T cell epitopes were identified using predictive algorithms and human leucocyte antigen (HLA)-binding assays. CD4+ T cell reactivity and IgE binding were assessed based on the induction of CD154 expression in peripheral blood mononuclear cells and using competitive ELISA assays, respectively. Results MS analysis of group 5 pollen allergens reveals considerable intra- and inter-species variability in amino acid sequence, with 30-50 predominant isoforms found for each species. Differences in the amino acid sequence as well as N- and O-glycosylation contribute to the variability of group 1 allergens, yielding 5-10 main isoforms, depending on the species. Out of 14 MHC class II-restricted T cell epitopes identified within group 1, only one is conserved among the five grass species. Significant differences in binding affinities for HLA-DR molecules result in variable CD4+ T cell recognition of group 1 and 5 allergens purified from the various species. Up to 38% and 85% of patients exhibit seric IgE responses to species-restricted (or semi-restricted) epitopes associated with group 1 or 5 allergens, respectively. Conclusion Major pollen allergens from distinct grass species bear both shared and species-restricted T and B cell immune epitopes. When compared with single extracts, a five grass pollen extract is thus more suitable for specific immunotherapy, as it contains a broader repertoire of the IgE epitopes to which patients are sensitized. Cite this as: H. Chabre, B. Gouyon, A. Huet, V. Baron-Bodo, E. Nony, M. Hrabina, F. Fenaille, A. Lautrette, M. Bonvalet, B. Maillere, V. Bordas-Le Floch, L. Van Overtvelt, K. Jain, E. Ezan, T. Batard and P. Moingeon, Clinical & Experimental Allergy, 2010 (40) 505-519.