Anti-CD63 antibodies suppress IgE-dependent allergic reactions in vitro and in vivo

Stefan Kraft, Tony Fleming, James M. Billingsley, Shih Yao Lin, Marie Hélène Jouvin, Peter Storz, Jean Pierre Kinet

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

High-affinity IgE receptor (FcεRI) cross-linking on mast cells (MCs) induces secretion of preformed allergy mediators (degranulation) and synthesis of lipid mediators and cytokines. Degranulation produces many symptoms of immediate-type allergic reactions and is modulated by adhesion to surfaces coated with specific extracellular matrix (ECM) proteins. The signals involved in this modulation are mostly unknown and their contribution to allergic reactions in vivo is unclear. Here we report the generation of monoclonal antibodies that potently suppress FcεRI-induced degranulation, but not leukotriene synthesis. We identified the antibody target as the tetraspanin CD63. Tetraspanins are membrane molecules that form multimolecular complexes with a broad array of molecules including ECM protein-binding β integrins. We found that anti-CD63 inhibits MC adhesion to fibronectin and vitronectin. Furthermore, anti-CD63 inhibits FcεRI-mediated degranulation in cells adherent to those ECM proteins but not in nonadherent cells. Thus the inhibition of degranulation by anti-CD63 correlates with its effect on adhesion. In support of a mechanistic linkage between the two types of inhibition, anti-CD63 had no effect on FcεRI-induced global tyrosine phosphorylation and calcium mobilization but impaired the Gab2-PI3K pathway that is known to be essential for both degranulation and adhesion. Finally, we showed that these antibodies inhibited FcεRI-mediated allergic reactions in vivo. These properties raise the possibility that anti-CD63 could be used as therapeutic agents in MC-dependent diseases.

Original languageEnglish (US)
Pages (from-to)385-396
Number of pages12
JournalJournal of Experimental Medicine
Volume201
Issue number3
DOIs
StatePublished - Feb 7 2005
Externally publishedYes

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Immunoglobulin E
Extracellular Matrix Proteins
Anti-Idiotypic Antibodies
Hypersensitivity
Mast Cells
Tetraspanins
Mastocytosis
Vitronectin
IgE Receptors
Cell Degranulation
Antibodies
Leukotrienes
Phosphatidylinositol 3-Kinases
Fibronectins
Protein Binding
Cell Adhesion
Integrins
Tyrosine
Monoclonal Antibodies
Phosphorylation

ASJC Scopus subject areas

  • Immunology

Cite this

Kraft, S., Fleming, T., Billingsley, J. M., Lin, S. Y., Jouvin, M. H., Storz, P., & Kinet, J. P. (2005). Anti-CD63 antibodies suppress IgE-dependent allergic reactions in vitro and in vivo. Journal of Experimental Medicine, 201(3), 385-396. https://doi.org/10.1084/jem.20042085

Anti-CD63 antibodies suppress IgE-dependent allergic reactions in vitro and in vivo. / Kraft, Stefan; Fleming, Tony; Billingsley, James M.; Lin, Shih Yao; Jouvin, Marie Hélène; Storz, Peter; Kinet, Jean Pierre.

In: Journal of Experimental Medicine, Vol. 201, No. 3, 07.02.2005, p. 385-396.

Research output: Contribution to journalArticle

Kraft, S, Fleming, T, Billingsley, JM, Lin, SY, Jouvin, MH, Storz, P & Kinet, JP 2005, 'Anti-CD63 antibodies suppress IgE-dependent allergic reactions in vitro and in vivo', Journal of Experimental Medicine, vol. 201, no. 3, pp. 385-396. https://doi.org/10.1084/jem.20042085
Kraft, Stefan ; Fleming, Tony ; Billingsley, James M. ; Lin, Shih Yao ; Jouvin, Marie Hélène ; Storz, Peter ; Kinet, Jean Pierre. / Anti-CD63 antibodies suppress IgE-dependent allergic reactions in vitro and in vivo. In: Journal of Experimental Medicine. 2005 ; Vol. 201, No. 3. pp. 385-396.
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