Allergome-wide peptide microarrays enable epitope deconvolution in allergen-specific immunotherapy

Area of Science:

• Immunology
• Allergology
• Proteomics

Background:

• Allergic reactions are initiated by allergen-specific IgE binding to effector cells.
• Antibodies of other isotypes, like IgG4, can modulate allergic responses.
• The structural complexity of allergen epitopes is not well understood.

Purpose of the Study:

• To characterize IgE, IgG4, and IgG epitope recognition across the allergome during allergen-specific immunotherapy (AIT).
• To investigate the global patterns of antibody responses to allergen epitopes during AIT.

Main Methods:

• Development of an allergome-wide microarray with over 172,000 overlapping peptides from 731 allergens.
• Analysis of IgE, IgG4, and IgG recognition in serum samples from patients undergoing AIT for pollen allergy.

Main Results:

• Significant induction of peptide-specific humoral immunity against Phl p 1 and Bet v 1 was observed during AIT.
• Epitope profiles were subject-specific and largely established within one year of AIT.
• Complex cross-reactivity patterns were identified, suggesting varied protection levels.

Conclusions:

• Allergen epitope recognition during AIT is complex and highly individualized.
• Epitope deconvolution is crucial for personalized analysis and understanding of AIT outcomes.