Interplay between Affinity and Valency in Effector Cell Degranulation: A Model System with Polcalcin Allergens and Human Patient-Derived IgE Antibodies

• Published in: The Journal of immunology (1950) 2019-10, Vol.203 (7), p.1693-1700
• Main Authors: Bucaite, Gintare, Kang-Pettinger, Tara, Moreira, Jorge, Gould, Hannah J, James, Louisa K, Sutton, Brian J, McDonnell, James M
• Format: Article
• Language: English
• Subjects: Allergens - genetics; Allergens - immunology; Antibody Affinity; Antigens, Plant - genetics; Antigens, Plant - immunology; Calcium-Binding Proteins - genetics; Calcium-Binding Proteins - immunology; Cell Degranulation; Epitopes - genetics; Epitopes - immunology; HEK293 Cells; Humans; Immunoglobulin E - immunology; Models, Immunological; Plant Proteins - genetics; Plant Proteins - immunology; Protein Multimerization - genetics; Protein Multimerization - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1900509

An allergic reaction is rapidly generated when allergens bind and cross-link IgE bound to its receptor FcεRI on effector cells, resulting in cell degranulation and release of proinflammatory mediators. The extent of effector cell activation is linked to allergen affinity, oligomeric state, valency, and spacing of IgE-binding epitopes on the allergen. Whereas most of these observations come from studies using synthetic allergens, in this study we have used Timothy grass pollen allergen Phl p 7 and birch pollen allergen Bet v 4 to study these effects. Despite the high homology of these polcalcin family allergens, Phl p 7 and Bet v 4 display different binding characteristics toward two human patient-derived polcalcin-specific IgE Abs. We have used native polcalcin dimers and engineered multimeric allergens to test the effects of affinity and oligomeric state on IgE binding and effector cell activation. Our results indicate that polcalcin multimers are required to stimulate high levels of effector cell degranulation when using the humanized RBL-SX38 cell model and that multivalency can overcome the need for high-affinity interactions.