TRANS-SIALIDASE, SAPA AMINO-ACID REPEATS AND THE RELATIONSHIP BETWEENTRYPANOSOMA-CRUZI AND THE MAMMALIAN HOST

During invasion of multicellular organisms, protozoan parasites expose functional molecules that become targets for the host immune response . Recent research on Trypanosoma cruzi, the agent of Chagas' disease, suggests a new model of how the parasite might deal with this problem. Several antigens of T. cruzi have tandemly repeated amino acid motifs in molecules with as yet unknown functions. In two cases, these repea ts are in molecules with a defined structure or function. Both protein s are implicated in the invasion of host-cells by the parasite. One of these is the core protein of a putative mucin-like glycoprotein that has Thr/Pro-rich repeats which, by themselves, might define the struct ure of a highly O-glycosylated molecule. The other protein is SAPA/tra ns-sialidase/neuraminidase, a molecule able to transfer sialic acid, t hat has so far only been described in trypanosomes. The amino acid rep eats present in SAPA/trans-sialidase/neuraminidase are unrelated to th e enzymic activity and constitute an immunodominant C-terminal domain. The N-terminal domain of SAPA/trans-sialidase/neuraminidase controls the enzymic activity since a recombinant molecule lacking the repeats conserves trans-sialidase activity. That both domains are functionally independent is also indicated by experiments that show that antibodie s directed against the amino acid repeats are unable to inhibit trans- sialidase activity. A large number of proteins having trans-sialidase related sequences but lacking enzymic activity are also present in the surface membrane of the parasite. The immunodominant SAPA/trans-siali dase/neuraminidase repeats, together with the complex network of cross -reacting epitopes present in related but enzymically inactive protein s might contribute to the delay in mounting an effective antibody resp onse. However, antibodies neutralizing trans-sialidase activity are ge nerated later during the infection. These antibody specificities are d irected to the enzymic domain of the molecule and might contribute to the control of parasite dissemination after the early period of the in fection.