THE USE OF MOUSE HUMAN CHIMERIC ANTIBODIES TO INVESTIGATE THE ROLES OF DIFFERENT ANTIBODY ISOTYPES, INCLUDING IGA2, IN THE KILLING OF SCHISTOSOMA-MANSONI SCHISTOSOMULA BY EOSINOPHILS

We report the use of a matched set of mice/human chimaeric antibodies, directed against the 5-iodo-4-hydroxyl-3-nitrophenacetyl (NIP) hapten, to investigate the roles of different human isotypes in antibody-mediated eosinophil-dependent killing of schistosomula. The chimaeric antibodies consist of mouse V(H), V(L) and C(L) regions with human gamma1, gamma2, gamma3 (2 allotypes), gamma4, alpha2, mu or epsilon C(H) regions and were used in in vitro assays with human eosinophils and NIP-coated S. mansoni schistosomula. Some anti-NIP isotypes mediated high levels of killing, which was specific for NIP-coated larvae, and we suggest that these antibodies will be a valuable tool for studies on the role of antibody isotypes in anti-schistosome immune effector mechanisms. In particular, this method directly demonstrated, for the first time, that IgA is highly effective in mediating the killing of metazoan parasites by human eosinophils.