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

TY - JOUR

T1 - Interplay between Affinity and Valency in Effector Cell Degranulation

T2 - A Model System with Polcalcin Allergens and Human Patient–Derived IgE Antibodies

AU - Bucaite, Gintare

AU - Kang-Pettinger, Tara

AU - Moreira, Jorge

AU - Gould, Hannah J.

AU - James, Louisa K.

AU - Sutton, Brian

AU - McDonnell, James M.

PY - 2019/10/1

Y1 - 2019/10/1

N2 - An allergic reaction is rapidly generated when allergens bind and crosslink immunoglobulin E bound to its receptor FcεRI on effector cells, resulting in cell degranulation and release of pro-inflammatory mediators. The extent of effector cell activation is linked to allergen affinity, oligomeric state, valency and spacing of IgE binding epitopes on the allergen. While most of these observations come from studies utilising synthetic allergens, here 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 towards two human patient-derived polcalcin-specific IgE antibodies. 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 humanised RBL-SX38 cell model, and that multivalency can overcome the need for high-affinity interactions.

AB - An allergic reaction is rapidly generated when allergens bind and crosslink immunoglobulin E bound to its receptor FcεRI on effector cells, resulting in cell degranulation and release of pro-inflammatory mediators. The extent of effector cell activation is linked to allergen affinity, oligomeric state, valency and spacing of IgE binding epitopes on the allergen. While most of these observations come from studies utilising synthetic allergens, here 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 towards two human patient-derived polcalcin-specific IgE antibodies. 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 humanised RBL-SX38 cell model, and that multivalency can overcome the need for high-affinity interactions.

UR - https://www.scopus.com/pages/publications/85072627745

U2 - 10.4049/jimmunol.1900509

DO - 10.4049/jimmunol.1900509

M3 - Article

SN - 0022-1767

VL - 203

SP - 1693

EP - 1700

JO - Journal of Immunology

JF - Journal of Immunology

IS - 7

ER -