What is an Allergen?

A food allergy occurs when the immune system mistakenly identifies specific proteins in food as harmful and launches an immune response. At the molecular level, this response is triggered by epitopes—specific sequences of amino acids within these food proteins—that bind to immune receptors and activate an allergic reaction.

Amino Acid Sequence and Immune Response

1. Protein Structure & Epitope Recognition
   • Food proteins are composed of long chains of amino acids, folded into specific three-dimensional structures.
   • Certain linear epitopes (continuous sequences of amino acids) or conformational epitopes (discontinuous sequences that form a recognizable structure) in these proteins can act as allergens.
2. Sensitization Phase (First Exposure)
   • When a person with a predisposition to allergies consumes the food, antigen-presenting cells (APCs), such as dendritic cells, process the protein and present epitope peptides to T-helper cells (Th2 subtype) via MHC class II molecules.
   • This leads to the production of cytokines like IL-4 and IL-13, which stimulate B cells to produce IgE antibodies specific to the allergenic protein.
3. Effector Phase (Subsequent Exposures)
   • Upon re-exposure to the allergenic protein, IgE antibodies (which are now bound to mast cells and basophils) recognize the specific amino acid sequences in the food protein.
   • This cross-linking of IgE receptors triggers degranulation, releasing histamine, leukotrienes, and prostaglandins, leading to symptoms like swelling, hives, or anaphylaxis.

Example: Peanut Allergy (Ara h Proteins)

• Peanut allergens include Ara h 1, Ara h 2, and Ara h 3.
• Ara h 2, for instance, contains multiple IgE-binding epitopes rich in hydrophobic and charged amino acids, which are highly stable and resistant to digestion, making them potent allergens.
• Specific sequences like DPYSPSQQ (in Ara h 2) bind strongly to IgE, triggering severe allergic responses.

Key Factors in Allergenic Amino Acid Sequences

• Hydrophobicity & Stability: Resistant to digestion (e.g., Ara h 2 and Ara h 6 from peanuts).
• Glycosylation & Cross-reactivity: Some allergens have glycoprotein modifications, enhancing their immune recognition.
• Highly Conserved Regions: Epitopes often occur in conserved protein regions, making them recognizable across similar allergens (e.g., caseins in milk).

Conclusion

Food allergies arise due to specific amino acid sequences in food proteins that bind to IgE and trigger immune activation. These epitopes play a key role in initiating both sensitization and allergic reactions, making sequence stability, structure, and immune binding affinity crucial in determining allergenicity.