Conformational vs Sequential Epitopes in Hen Egg Allergy
Sequential (linear) epitopes of hen egg proteins, particularly ovomucoid, are strongly associated with persistent egg allergy, while conformational epitopes are more commonly recognized in transient egg allergy that resolves with age. 1
Clinical Significance of Epitope Recognition
Sequential Epitopes and Persistent Allergy
- IgE antibodies targeting sequential epitopes of ovomucoid serve as markers for persistent egg allergy. 1
- Children with long-lasting egg allergy demonstrate significantly higher IgE concentrations against both sequential and native (conformational) ovomucoid and ovalbumin compared to those who subsequently develop tolerance (P < 0.01). 1
- Four major sequential IgE-binding epitopes in ovomucoid (amino acids 1-10,9-20,47-56, and 113-124) were recognized by all seven patients with persistent egg allergy, whereas none of the 11 children who outgrew their allergy recognized these epitopes. 1
- Detection of specific IgE against linear epitopes from Gal d 1 (ovomucoid) has additional diagnostic value in identifying hen's egg allergic adults with objective symptoms. 2
Conformational Epitopes and Transient Allergy
- Conformational epitopes appear more important for Gal d 3 (ovalbumin) recognition, with only a few linear epitopes detected, suggesting greater reliance on three-dimensional protein structure. 2
- The conformational stability of hen egg lysozyme inversely correlates with its capacity to induce type 2 T-helper (Th2) immune responses and IgE antibody production—less stable proteins with intact conformational structure are more allergenic. 3
- Both conformational and sequential epitopes exist on ovalbumin, with seven different epitopes identifiable on native ovalbumin and four on denatured non-reduced ovalbumin. 4
Practical Diagnostic Implications
For Predicting Persistent vs Transient Allergy
- Screen for IgE antibodies to specific sequential epitopes of ovomucoid (particularly aa30-41, aa39-50, or aa84-95 for Gal d 1) to identify patients likely to have persistent egg allergy. 2, 1
- Clinically relevant sensitization to Gal d 1 was confirmed by IgE-binding to these linear epitopes in 6/13 allergic adults with objective symptoms, compared to only 1/15 tolerant patients. 2
- Patients with persistent egg allergy develop IgE antibodies against more sequential AND conformational epitopes, indicating broader epitope recognition. 1
Immunodominant Epitope Regions
- Five distinct regions contain dominant allergic IgE epitopes in ovalbumin: L38-T49, D95-A102, E191-V200, V243-E248, and G251-N260. 5
- These epitopes are composed primarily of hydrophobic amino acids, followed by polar and charged residues, with structures consisting of beta-sheet, beta-turn, and one alpha-helix (D95-A102). 5
- The two largest CNBr-fragments of ovalbumin (residues 41-172 and 301-385) bind both monoclonal antibodies and patients' IgE, representing key immunogenic structures. 4
Tolerance Development and Epitope Recognition
Natural Tolerance Acquisition
- Children who acquired natural tolerance to cow's milk had IgE and IgG4 antibodies that more often recognized the same sequential epitopes, with both IgE and IgG4 binding intensity decreasing significantly from baseline until tolerance development. 6
- This pattern suggests that tolerance involves coordinated changes in both IgE and IgG4 responses to sequential epitopes rather than complete loss of epitope recognition. 6
Clinical Pitfall to Avoid
- Do not rely solely on total IgE or sIgE levels to egg extracts or components, as these overlap substantially between allergic and tolerant adults. 2
- The sIgE/sIgG4 ratio to Gal d 1, while having an increased median in allergic adults, shows comparable ranges between allergic and tolerant groups, limiting its discriminatory value. 2
- Component-resolved diagnosis with epitope mapping provides superior specificity for identifying clinically relevant egg allergy, particularly in adults with objective symptoms. 2