Targeted elimination of cells expressing the high-affinity receptor for IgE (FcεRI) by a Pseudomonas exotoxin-based chimeric protein

The interaction between IgE and its high-affinity receptor FcεRI found on mast cells and basophils is the primary effector pathway in allergic response. To achieve a targeted elimination of cells expressing FcεRI receptors, we constructed a chimeric protein in which a Fc fragment of mouse IgE is attached to a truncated form of Pseudomonas exotoxin (PE). To prepare the targeting moiety, we used a DNA sequence corresponding to amino acids 301-437, representing 30 residues of domain 2 and domain 3 of the mouse IgE constant region. This sequence was fused at the 5' of a cDNA encoding PE₄₀, a truncated form of PE lacking the cell binding domain. The chimeric protein, termed FC(2'-3)-PE₄₀, was expressed in Escherichia coli and partially purified. The protein is highly cytotoxic to mouse mast cell lines and bone marrow-derived primary mast cells. This cytotoxicity is specific, as it could be blocked upon addition of whole IgE. Moreover, the protein had no effect on other cell lines of hemopoietic origin. The Fc(2'-3)-PE₄₀ chimeric protein offers a new approach to the treatment of allergic disorders.