IDENTIFICATION OF RECOMBINANT FILARIAL PROTEINS CAPABLE OF INDUCING POLYCLONAL AND ANTIGEN-SPECIFIC IGE AND IGG4 ANTIBODIES

Filarial infection is characterized by an immune response associated w ith the production of Ag-specific IgG4 and IgE and IL-4 and IL-5. To i dentify filarial Ags capable of inducing such responses and to analyze the role Ags themselves play in sustaining it, 24 recombinant filaria l parasite proteins were screened for their ability to be recognized b y sera from 67 individuals with tissue-invasive filarial infections. A mong the recombinant proteins that were recognized by IgG4 or IgE Abs in 25% of the sera or more, two were selected on the basis of their ab ility to elicit polyclonal and Ag-specific IgE/IgG4 Abs in vitro. Ov27 (analogous to Ov7/cystatin, a cysteine protease inhibitor) and OvD5B (analogous to Ov33, an aspartyl protease inhibitor) induced both a pol yclonal and Ag-specific IgE/IgG4 response that was blocked by neutrali zing Abs to IL-4 and to IL-13 or by soluble IL-4 receptors. Recombinan t human IFN-gamma and IL-12 also led to a decrease in the production o f polyclonal and Ag-specific IgE/IgG4 Abs. In addition, these two reco mbinant proteins preferentially stimulated the secretion of IL-4, IL-5 , and IL-10 (in contrast to IFN-gamma). The data suggest that certain epitopes on filarial Ags preferentially elicit a Th2-type response and provide an in vitro model for dissecting the mechanisms underlying th is preferential response.