Identification of Trypanosoma cruzi trans-sialidase family members as targets of protective CD8+ TC1 responses

Abstract

CD8+ T lymphocytes play a critical role in immunity to Trypanosoma cruzi. However, the target molecules of this T cell subset have not been elucidated. In this work, we report the identification of an H-2Kb-restricted CTL epitope within two trypomastigote surface Ags encoded by members of the T. cruzi sialidase/trans-sialidase gene superfamily. Octapeptide VDYNFTIV sensitized target cells for lysis by CD8+ CTL generated from spleens of T. cruzi-infected mice. Peptide-specific CD8+ T cell lines were cytotoxic, secreted IFN-gamma and TNF-alpha, but low to undetectable levels of IL-4 and IL-5, and were able, upon adoptive transfer, to confer a high degree of protection against challenge infection. Finally, the protective determinant appears to be conserved among parasites from diverse geographic locations. This constitutes the first identified class I MHC-restricted epitope in T. cruzi and provides the basis for the search of additional targets to be considered in the development of vaccines against Chagas' disease.