The B subunit of shiga toxin fused to a tumor antigen elicits CTL and targets dendritic cells to allow MHC class I-restricted presentation of peptides derived from exogenous antigens

Citation
N. Haicheur et al., The B subunit of shiga toxin fused to a tumor antigen elicits CTL and targets dendritic cells to allow MHC class I-restricted presentation of peptides derived from exogenous antigens, J IMMUNOL, 165(6), 2000, pp. 3301-3308
Citations number
63
Categorie Soggetti
Immunology
Journal title
JOURNAL OF IMMUNOLOGY
ISSN journal
00221767 → ACNP
Volume
165
Issue
6
Year of publication
2000
Pages
3301 - 3308
Database
ISI
SICI code
0022-1767(20000915)165:6<3301:TBSOST>2.0.ZU;2-B
Abstract
Immunization with peptide or recombinant proteins generally fails to elicit CTL, which are thought to play a key role in the control of virus-infected cells and tumor growth. In this study we show that the nontoxic B subunit of Shiga toxin fused to a tumor peptide derived from the mouse mastocytoma P815 can induce specific CTL in mice without the use of adjuvant, The Shiga B subunit acts as a vector rather than as an adjuvant, because coinjection of the tumor peptide and the B subunit as separate entities does not lead to CTL induction. We also demonstrated that in vitro the B subunit mediates the delivery of various exogenous CDS T cell epitopes into the conventiona l MHC class I-restricted pathway, as this process is inhibited by brefeldin A and lactacystin and requires a functional TAP system. In contrast to oth er nonviral methods for transport of exogenous Ags into the endogenous MHC class I pathway that involve macropinocytosis or phagocytosis, the Shiga B subunit targets this pathway in a receptor-dependent manner, namely via bin ding to the glycolipid Gb3, Because this receptor is highly expressed on va rious dendritic cells, it should allow preferential targeting of the Shiga B subunit to these professional APCs, Therefore, the Shiga B subunit appear s to represent an attractive vector for vaccine development due to its abil ity to target dendritic cells and to induce specific CTL without the need f or adjuvant.