Isolation and characterization of a 92-KD surface molecule of Trypanosoma cruzi amastigotes recognized by a monoclonal antibody that induces complement-mediated killing.
The presence of lytic antibodies in the circulation of patients with chronic Chagas' disease might lead to their cure. It has been shown that amastigotes of Trypanosoma cruzi activate complement and accumulate large amounts of the terminal complement components, but without killing the parasites. One plausible explanation for this observation is that the insertion of the membrane attack complex of complement is prevented by inhibitors present in the parasite membrane. To explore this possibility, we raised a panel of monoclonal antibodies (MAbs) against the surface molecules of T. cruzi amastigotes. One of these, MAb M4C12, induced complement-mediated lysis of amastigotes as detected with a 86Rb-release assay. The antigen molecule from the membrane lysate of amastigotes that was recognized by MAb M4C12 was purified, characterized, and designated M4C12Ag. It is a 92-kD molecule structurally related to Ssp4, a previously characterized amastigote surface molecule. However, M4C12Ag is more basic (pI 6.9-7.1) than Ssp4 (pI 5.2-6.0), and is larger (92 kD) than Ssp4 (70 kD and 84 kD). Purified M4C12Ag did not inhibit the terminal components of complement when tested in hemolytic assays. This molecule may not be an inhibitor of complement, yet it is certainly an amastigote-specific surface molecule with immunologic importance because it is the only molecule that could induce formation of a lytic antibody.
Iida
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Department of Pathology, New York University, School of Medicine, New York.
Ley
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000953:Antigens, Protozoan / Q000276:immunology / Q000302:isolation & purification*; D000954:Antigens, Surface / Q000276:immunology / Q000302:isolation & purification*; D003167:Complement Activation / Q000276:immunology*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D014349:Trypanosoma cruzi / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000953:Antigens, Protozoan; D000954:Antigens, Surface