Trans-sialidase, SAPA amino acid repeats and the relationship betweenTrypanosoma cruziand the mammalian host

Abstract

SUMMARYDuring invasion of multicellular organisms, protozoan parasites expose functional molecules that become targets for the host immune response. Recent research onTrypanosoma cruzi, the agent of Chagas' disease, suggests a new model of how the parasite might deal with this problem. Several antigens ofT. cruzihave tandemly repeated amino acid motifs in molecules with as yet unknown functions. In two cases, these repeats are in molecules with a defined structure or function. Both proteins 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 structure of a highlyO-glycosylated molecule. The other protein is SAPA/trans-sialidase/neuraminidase, a molecule able to transfer sialic acid, that has so far only been described in trypanosomes. The amino acid repeats present in SAPA/trans-sialidase/neuraminidase are unrelated to the 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 antibodies 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-sialidase/neuraminidase repeats, together with the complex network of cross-reacting epitopes present in related but enzymically inactive proteins might contribute to the delay in mounting an effective antibody response. However, antibodies neutralizing trans-sialidase activity are generated later during the infection. These antibody specificities are directed to the enzymic domain of the molecule and might contribute to the control of parasite dissemination after the early period of the infection.