Identification of Trypanosoma cruzi trans-sialidase family members as targets of protective CD8+ TC1 responses.
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.
Wizel
B
B
Department of Cellular Biology, University of Georgia, Athens 30602, USA.
Nunes
M
M
Tarleton
R L
RL
D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D002460:Cell Line; D014355:Chagas Disease / Q000276:immunology* / Q000401:mortality / Q000469:parasitology / Q000517:prevention & control; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D005260:Female; D006023:Glycoproteins / Q000008:administration & dosage / Q000276:immunology*; D006183:H-2 Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D009439:Neuraminidase / Q000008:administration & dosage / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D013045:Species Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D014349:Trypanosoma cruzi / Q000201:enzymology* / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000953:Antigens, Protozoan; D016207:Cytokines; D006023:Glycoproteins; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; C069715:trans-sialidase; D009439:Neuraminidase