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

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. Maillère, V. Bordas‐Le Floch, L. Van Overtvelt, K. Jain, E. Ezan, T. Batard and P. Moingeon, Clinical & Experimental Allergy, 2010 (40) 505–519.