To cite this article: Mueller GA, Gosavi RA, Pomés A, Wünschmann S, Moon AF, London RE, Pedersen LC. Ara h 2: crystal structure and IgE binding distinguish two subpopulations of peanut allergic patients by epitope diversity. Allergy 2011; 66: 878–885.

Background:  Peanut allergy affects 1% of the population and causes the most fatal food‐related anaphylactic reactions. The protein Ara h 2 is the most potent peanut allergen recognized by 80–90% of peanut allergic patients.

Methods:  The crystal structure of the major peanut allergen Ara h 2 was determined for the first time at 2.7 Å resolution using a customized maltose‐binding protein (MBP)‐fusion system. IgE antibody binding to the MBP fusion construct vs the natural allergen was compared by ELISA using sera from peanut allergic patients.

Results:  The structure of Ara h 2 is a five‐helix bundle held together by four disulfide bonds and related to the prolamin protein superfamily. The fold is most similar to other amylase and trypsin inhibitors. The MBP–Ara h 2 fusion construct was positively recognized by IgE from 76% of allergic patients (25/33). Two populations of patients could be identified. Subpopulation 1 (n = 14) showed an excellent correlation of IgE antibody binding to natural vs recombinant Ara h 2. Subpopulation 2 (n = 15) showed significantly reduced IgE binding to the MBP fusion protein. Interestingly, about 20% of the IgE binding in subpopulation 2 could be recovered by increasing the distance between MBP and Ara h 2 in a second construct.

Discussion:  The reduced IgE binding to the MBP–Ara h 2 of subpopulation 2 indicates that the MBP molecule protects an immunodominant epitope region near the first helix of Ara h 2. Residues involved in the epitope(s) are suggested by the crystal structure. The MBP–Ara h 2 fusion constructs will be useful to further elucidate the relevance of certain epitopes to peanut allergy.