Genetic immunization based on the ubiquitin-fusion degradation pathway against Trypanosoma cruzi.

Abstract

Cytotoxic CD8(+) T cells are particularly important to the development of protective immunity against the intracellular protozoan parasite, Trypanosoma cruzi, the etiological agent of Chagas disease. We have developed a new effective strategy of genetic immunization by activating CD8(+) T cells through the ubiquitin-fusion degradation (UFD) pathway. We constructed expression plasmids encoding the amastigote surface protein-2 (ASP-2) of T. cruzi. To induce the UFD pathway, a chimeric gene encoding ubiquitin fused to ASP-2 (pUB-ASP-2) was constructed. Mice immunized with pUB-ASP-2 presented lower parasitemia and longer survival period, compared with mice immunized with pASP-2 alone. Depletion of CD8(+) T cells abolished protection against T. cruzi in mice immunized with pUB-ASP-2 while depletion of CD4(+) T cells did not influence the effective immunity. Mice deficient in LMP2 or LMP7, subunits of immunoproteasomes, were not able to develop protective immunity induced. These results suggest that ubiquitin-fused antigens expressed in antigen-presenting cells were effectively degraded via the UFD pathway, and subsequently activated CD8(+) T cells. Consequently, immunization with pUB-ASP-2 was able to induce potent protective immunity against infection of T. cruzi.

DOI: 10.1016/j.bbrc.2009.12.166

Cite this paper

@article{Chou2010GeneticIB, title={Genetic immunization based on the ubiquitin-fusion degradation pathway against Trypanosoma cruzi.}, author={Bin Chou and Kenji Hiromatsu and Hajime Hisaeda and Xuefeng Duan and Takashi Imai and Shigeo Murata and Keiji Tanaka and Kunisuke Himeno}, journal={Biochemical and biophysical research communications}, year={2010}, volume={392 3}, pages={277-82} }