Isoforms of the Major Peanut Allergen Ara h 2: IgE Binding in Children with Peanut Allergy (1)
Seven peanut allergens have been characterized by cDNA cloning (Ara h 1–7) and their relative importance is determined by IgE binding studies. Ara h 2.0201 could be a more potent allergen than the original Ara h 2.0101. An important feature of the Ara h 2 immunodominant IgE epitopes is that they are resistant to trypsin digestion and are more likely to remain intact in the gastrointestinal tract.
Ara h 2.0201 had the expected insertion of 12 amino acids as well as substitutions of glycine (G) for glutamic acid (E) at position 40 and glutamic acid (E) for aspartic acid (D) at position 142.
The 12-amino acid insert here would be the previously proposed QDPDRRDPYSPS. The Ara h 2.0201 isoform contains an additional copy of the immunodominant IgE epitope DPYSPS compared to the original sequence regardless of where the insert/deletion is positioned.
The frequency of IgE reactivity was 77.1% (54/70) for Ara h 2.0101 and 81.4% (57/70) for Ara h 2.0201 and the means were similar.
The correlation between Ara h 2.0101 and Ara h 2.0201 was extremely strong (r = 0.987, p < 0.0001). Ara h 2.0201 was able to inhibit IgE reactivity to both isoforms to a similar degree but although Ara h 2.0101 was as efficient as Ara h 2.0201 in blocking IgE binding to itself, it was less effective at inhibiting IgE binding to Ara h 2.0201.
Ara h 2.0201 has an insert of 12 amino acids that contains an extra copy of the sequence DPYSPS, which has been described as an immunodominant IgE epitope. There are 2 copies of this motif in Ara h 2.0101 and 3 copies in Ara h 2.0201. Ara h 2.0101 was not as efficient at blocking reactivity to Ara h 2.0201 indicating there is an additional IgE specificity for the Ara h 2.0201 isoform. This region may be important for T cell reactivity.