Mapping Allergen B- and T-Cell Epitopes: Technological Advances and Their Role in Precision Allergy Therapy.

Abstract

Allergic diseases arise from aberrant immune recognition of otherwise harmless environmental proteins and are driven by epitope-specific interactions between allergens and the adaptive immune system. Although component-resolved diagnostics have improved molecular characterisation of sensitization, they remain limited to whole-allergen resolution and do not capture the fine specificity and heterogeneity of immune recognition that ultimately determine clinical reactivity, cross-reactivity, and treatment outcomes. Increasing evidence indicates that allergic sensitization, severity, and tolerance are governed by discrete B- and T-cell epitopes rather than entire allergen molecules. This review provides a comprehensive overview of established and emerging technologies for allergen epitope mapping at molecular resolution. For B-cell epitopes, we discuss peptide-based screening approaches, display technologies, deep mutational scanning, structural and biophysical methods, and advances in in silico prediction. For T-cell epitopes, we summarise experimental and computational strategies to identify allergen-derived peptides presented by HLA molecules and recognised by T-cell receptors, highlighting the influence of HLA diversity on individualised immune responses. Finally, we explore the clinical and translational implications of epitope-resolved allergen profiling for next-generation diagnostics, functional cell-based assays, improved risk stratification, cross-reactivity prediction, and the rational design of safer and more precise immunotherapies. Together, these approaches support the development of precision medicine strategies in allergic disease.