Cleavage of human IgE mediated by Schistosoma mansoni

Background: IgE-mediated mechanisms are important in protection against hel minth parasites. However, schistosomes are long-lived in mammalian hosts, p resumably as a result of immune evasion strategies. We sought evidence for one such strategy, namely specific cleavage of host IgE. Methods: Human IgE , IgA and IgG were incubated with extracts from cercarial and schistosomula r stages of Schistosoma mansoni or with schistosomular culture supernatants . The resulting products were analysed by Western blotting with Ig-specific antibodies. Numerous protease inhibitors were assessed for ability to inhi bit the observed cleavage of IgE by the extracts. Partial purification of t he IgE-proteolytic activity from cercarial extract was achieved by gel filt ration. To test IgE function, we compared the abilities of untreated and sc histosomular-treated IgE to mediate rosette formation through interaction w ith Fc epsilon receptors. Results: Cercarial and schistosomular extracts we re found to cleave human, mouse and rat IgE but not human IgA1, IgA2 or IgG 1. Schistosomular culture supernatants displayed similar proteolytic activi ty towards IgE. Immunoblotting suggested that cleavage occurred close to th e C epsilon 2/C epsilon 3 domain interface of the IgE heavy chain. PMSF and elastatinal inhibited cleavage, suggesting that the protease involved is a n elastase-like serine protease, particularly since porcine pancreatic elas tase also cleaved IgE to give similar-sized products. Further, the chlorome thyl ketone derivatized peptide MeO-Suc-Ala-Ala-Pro-Leu-CMK, known to speci fically inhibit the schistosome elastase, prevented IgE cleavage. Cleavage of human IgE rendered the antibody molecule unable to interact with U937 ce lls expressing Fc epsilon RII. Conclusions: An elastase-like protease in S. mansoni is able to render IgE nonfunctional. (C) 2000 S. Karger AG, Basel.