NOVEL MECHANISMS OF IMMUNE EVASION BY SCHISTOSOMA-MANSONI

The interaction of Schistosoma mansoni with ifs host's immune system i s largely affected by multiple specific and non-specific evasion mecha nisms employed by the parasite to reduce the host's immune reactivity. Only little is known about these mechanisms on the molecular level. T he four molecules described below are intrinsic parasitic proteins rec ently identified and studied in our laboratory. 1. m28 - A 28kDa membr ane serine protease. m28 cleaves iC3b and can thus restrict attack by effector cells utilizing complement receptors (especially CR3). Treatm ent with protease inhibitors potentiates killing of schistosomula by c omplement plus neutrophils. 2. Smpi56 - A 56kDa serine protease inhibi tor Smpi56 binds covalently to m28 and to neutrophil 's elastase and b locks their proteolytic activity. 3. P70 - A 70kDa C3b binding protein . The postulated activity of P70 includes binding to C3b and blocking of complement activation at the C3 step. 4. SCIP-1 - A 94kDa schistoso me complement inhibitor SCIP-1 shows antigenic and functional similari ties to the human 18kDa complement inhibitor CD59. Like CD59, SCIP-1 b inds to C8 and C9 and blocks formation of the complement membrane atta ck complex. Antibodies directed to human CD59 bind to schistosomula an d potentiate their killing by complement. The structure and function o f these four proteins as well as their capacity to induce protection f rom infection with S. mansoni are under investigation.