Trypanosoma cruzi, the agent of
Chagas' disease, expresses
trans-sialidase, a unique
enzyme activity that enables the parasite to invade host cells by transferring sialyl residues from host glyconjugates to the parasite's surface acceptor molecules. The
enzyme is also shed into the surrounding environment, causing apoptosis in cells from the immune system. During
infections, an antibody response against the catalytic region of the
trans-sialidase that is coincident with the control of the
parasitemia and survival of the host is observed. This low-titer humoral response is characterized by its persistence for many years in
benznidazole-treated patients. Here we analyzed the antigenic structure of the molecule by phage-displayed
peptide combinatorial libraries and SPOT synthesis. Several
epitopes were defined and located on the three-dimensional model of the
enzyme. Unexpectedly, cross-reaction was found among several
epitopes distributed in different locations displaying nonconsensus sequences. This finding was confirmed by the reactivity of three
monoclonal antibodies able to recognize non-sequence-related
peptides that together constitute the surface surrounding the catalytic site of the
enzyme. The presence of cross-reacting
epitopes within a single molecule suggests a mechanism developed to avoid a strong humoral response by displaying an undefined target to the immune system.