Occurrence of mouse α2-macroglobulin antigenic determinants of Schistosoma mansoni adults, with evidence on their nature.

Rabbits immunized with washed, homogenized adult Schistosoma mansoni worms recovered from mice (mouse worms) developed precipitins which reacted with mouse yG2 and mouse ca-macroglobulin (a2M). Both antibodies could be absorbed from the rabbit antisera with mouse worms or mouse serum. Only the anti-o_M could be absorbed with monkey worms. Rhesus monkeys immunized with purified mouse a2M and subsequently challenged with mouse worms surgically implanted in their hepatic portal systems did not show an increased ability to destroy the mouse worms. Direct identification of mouse a2M antigenic determinants on the worms' surfaces was made by mixed agglutination modified for use with mouse o2M-coated red cells. Both male and female worms possess the determinants, with male worms apparently having more. As demonstrated by mixed agglutination, mouse worms, monkey worms, and mouse worms recovered after 1 month in rhesus monkeys were all alike in possessing mouse acM antigenic determinants. Because of the lack of cross-reactivity between primate and murine c2-macroglobulins and because mouse a2M antigenic determinants are also found on monkey worms, it is concluded that these shared host-parasite antigenic determinants are constitutive determinants synthesized by the schistosome. Interest in host or hostlike antigenic determinants in Schistosoma mansoni (Capron et al., 1965, 1968; Damian, 1964, 1967) has accelerated with the evidence from Smithers' laboratory that schistosomes acquire "host" antigens, both in vivo (Smithers et al., 1969; Clegg et al., 1970) and in vitro (Clegg et al., 1971). Various theories have been advanced to explain host-parasite antigen sharing. Antigen mimicry theories, e.g., those suggesting that there are constitutive hostlike determinants synthesized by parasites (Sprent, 1962; Dineen, 1963; Damian, 1964), are not supported by the evidence that certain "host" antigens, disclosed by heterologous host transfer experiments, are evanescent (Smithers et al., 1969). Rather, this evidence favors equally an antigen incorporation theory (Smithers et al., 1968) and the theory of host-specific antigen synthesis by the parasite through a host-triggered induction process (Capron et al., 1968). The present investigations of host-parasite antigen sharing were stimulated by the observation of one of us (W.J.H.) that rabbits imReceived for publication 11 April 1972. * This investigation was supported by the United States-Japan Cooperative Medical Science Program administered by the NIAID, NIH, Department of Health, Education and Welfare, Grant 5 R22 AI08398. munized with homogenized adult schistosomes recovered from mice (mouse worms) developed precipitins reactive with a mouse serum aglobulin. This protein was subsequently characterized and identified as x2-macroglobulin (a2M) by Greene et al. (1971). When first noted, it was thought that the protein represented the acquired mouse determinants that Smithers et al. (1969) demonstrated by surgically transferring mouse worms into "antimouse" monkeys. The research reported herein was designed to test this hypothesis and to provide further information on the nature of the determinants in question. MATERIALS AND METHODS A Kenyan strain of Schistosoma mansoni was used. It was originally isolated from a patient and subsequently passaged through mice and hamsters, but since establishment in our laboratory in 1968, the parasite has been maintained exclusively by passage through Biomphalaria pfeifferi and savanna baboons (Papio cynocephalus). Mice and rhesus monkeys were infected from the maintenance stock only as needed for specific experiments. Adult worms were recovered from mice and rhesus monkeys by modifications of the "perf-o-suction" perfusion method (Radke et al., 1961). Worms to be used for immunogen, antiserum absorptions, surgical transfers, or in vitro tests were transferred from the perfusion fluid to phosphate-buffered (pH 7.4, 0.01 M) saline (PBS) and teased free of any adhering debris under a stereoscopic micro-