Humanized anti-IgE mAb Hu-901 prevents the activation of allergen-specific T cells.
BACKGROUND
As a result of the very efficient capture of allergens by IgE that focuses to CD23 on B cells or FcepsilonRI on dendritic cells, allergen-specific T cells can be activated after exposure to very low levels of allergens. This IgE-mediated allergen presentation is 100- to 1,000-fold more efficient than fluid phase endocytosis. The aim of the present study was to determine whether humanized anti-IgE mAb Hu-901 can prevent the activation of allergen-specific T cells by inhibiting IgE-mediated allergen presentation.


METHODS
A house dust mite major allergen Der p 1-specific T cell line was generated from an allergic asthma patient, and a model was set up to show IgE-facilitated allergen presentation via CD23 on EBV-transformed B cells. In addition, experiments were performed by FACS analysis, detecting the presence of IgE-allergen complexes bound to EBV-B cells by polyclonal FITC-labeled anti-IgE antisera.


RESULTS
The anti-IgE mAb Hu-901 inhibited proliferation of allergen-specific T cells at low allergen concentrations. Inhibition was dose-dependent. This effect could be explained by Hu-901 inhibition of binding of allergen-IgE complexes to CD23 expressed on EBV-transformed B lymphocytes.


CONCLUSIONS
These data clearly indicate that anti-IgE antibodies for the treatment of allergy exert their effect not only by inhibiting mast cell/basophil degranulation, but also by preventing T cell activation, which possibly explains the effect of anti-IgE treatment on late-phase reactions noted in clinical studies.
van Neerven
R J
RJ
Tanox Pharma BV, Amsterdam, The Netherlands. joostvanneerven@tanox.nl
van Roomen
C P
CP
Thomas
W R
WR
de Boer
M
M
Knol
E F
EF
Davis
F M
FM
D000485:Allergens / Q000276:immunology; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D017951:Antigen Presentation; D039741:Antigens, Dermatophagoides; D002460:Cell Line; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000276:immunology
D000485:Allergens; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D039741:Antigens, Dermatophagoides; D006023:Glycoproteins; C026408:anti-IgE antibodies