The mast cell binding site on human immunoglobulin E

Birgit Helm, Philip Marsh, Donata Vercelli, Eduardo Padlan, Hannah Gould, Raif Geha

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122 Scopus citations

Abstract

Antibodies of the immunoglobulin E isotype sensitize mast cells and basophils for antigen-induced mediator release by binding through the Fc portion to a high-affinity receptor (FcεRl, Ka = 10 9 M-1) on the cell surface1,2 causing the clinical manifestations of type I hypersensitivity. As the amino acid sequence of the human epsilon chain is now known3, attempts have been made to map the FcεRl binding site on IgE to a fragment smaller than Fcε using proteolytic cleavage products, none of which proved to be active3. Cleavage between the Cε2 and C ε3 domains released two inactive fragments, suggesting that the junction between these segments could be important in receptor binding 3. This region is protected against protease digestion in the rat IgE complex with the receptor of rat basophilic leukaemia cells4. Here we report the mapping of the mast cell receptor binding site on human IgE to a sequence of 76 amino acids at the Cε2/Cε 3 junction. Recombinant peptides containing this sequence inhibit passive sensitization of skin mast cells in vivo and sensitize mast cells to degranulation by anti-IgE in vitro almost as efficiently as a myeloma IgE. Fragments containing the separate domains are inactive. Additional sequences are required for rapid assembly of fragments into disulphide-linked dimers, suggesting that a single chain can form the active site. In a three-dimensional model of the human Fcε, the two identical segments are far apart. Each folds to generate a cleft between the Cε2 and C ε3 domains on the surface of the Fcε. The docking of IgE on to mast cells could take place within this cleft.

Original languageEnglish (US)
Pages (from-to)180-183
Number of pages4
JournalNature
Volume331
Issue number6152
DOIs
StatePublished - Jan 1 1988
Externally publishedYes

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    Helm, B., Marsh, P., Vercelli, D., Padlan, E., Gould, H., & Geha, R. (1988). The mast cell binding site on human immunoglobulin E. Nature, 331(6152), 180-183. https://doi.org/10.1038/331180a0