Submitted to: American Chemical Society Abstracts
Publication Type: Abstract Only
Publication Acceptance Date: 5/26/2022
Publication Date: N/A
Interpretive Summary: Peanuts are a common cause of food allergy in children, and the occurrence of peanut allergy in the pediatric population has increased in recent decades. Immunoglobulin-E (IgE) is a specific type of antibody that causes allergic reactions. IgE binding to peanut allergens triggers cells to release molecules that alter respiratory and cardiovascular system functions and can lead to life-threatening reactions. Peanuts have several proteins that act as allergens, and one of them is the Ara h 2 protein. Ara h 2 has a well-characterized protein structure and linear amino acid sequence.IgE can bind to linear peptides made of Ara h 2 amino acids and three-dimensional patches on the surface of the Ara h 2 protein. These surface patches are called conformational epitopes. Computer modeling was used to generate three-dimensional tructures of IgE from peanut allergic volunteers and then predict what conformational epitopes these IgE antibodies would bind on Ara h 2. The modeling suggests two potential conformational epitopes on the Ara h 2 protein where these IgE antibodies may bind. The two predicted conformational epitopes are close to one another but are distinct. Characterizing these conformational epitopes will help identify what characteristics make these proteins commonly act as allergens. However, more IgE antibody sequences from peanut allergic volunteers are needed to increase confidence in the conformational epitope predictions presented here.
Technical Abstract: Peanut allergy is the most common food allergy in children, and the incidence of peanut allergy in the pediatric population has increased in recent decades. Immunoglobulin-E (IgE) binding to peanut allergens triggers mast cell and basophil activation and the release of vasoactive mediators that can compromise the respiratory and cardiovascular systems. The Ara h 2 peanut allergen is a relatively small (17 kDa) 2S albumin that is commonly bound by IgE from peanut allergic volunteers. The Ara h 2 protein has a well-defined and highly conserved structure composed of five alpha helices held together by four disulfide bonds. Linear peptide epitope mapping studies may not provide a complete picture of the contribution of conformational epitopes to IgE-allergen interactions. A few peanut allergic IgE antibody sequences are publicly available, and they were modeled and used in docking studies to the Ara h 2 immunodominant peanut allergen to identify possible conformational epitopes. Protein structure preparation steps were performed in Molecular Operating Environment (MOE)using a crystal structure of recombinant Ara h 2 fused to maltose binding protein (pdb 30B4). IgE antibodies were modeled in MOE using the antibody modeler function using the best fit framework and complementarity-determining regions (CDRs). The modeling suggests two potential conformational epitopes where these IgE antibodies may bind to Ara h 2. The first predicted conformational epitope consists of residues within alpha helix one, including Arg31 and Arg32 near the amino terminus of the protein, and residues Arg115 and Glu119 within alpha helix four. The second predicted conformational epitope consists of three asparagine residues in helix three (Asn105, 108, and112) and loop residues Arg155 and Gln158 near the carboxy terminus. More IgE antibody sequences from peanut allergic volunteers are needed to increase confidence in the conformational epitope predictions presented here.