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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.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Chou B,Hiromatsu K,Hisaeda H,Duan X,Imai T,Murata S,Tanaka K,Himeno K

doi

10.1016/j.bbrc.2009.12.166

subject

Has Abstract

pub_date

2010-02-12 00:00:00

pages

277-82

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(10)00007-0

journal_volume

392

pub_type

杂志文章

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