Effective CD8(+) T cell priming and tumor protection by enterotoxin B subunit-conjugated peptides targeted to dendritic cells.
In our previous studies we have shown that bacterial enterotoxin B subunits are effective vehicles to deliver antigen into the MHC class I processing route. Here we have used the non-toxic Escherichia coli heat labile enterotoxin B subunit (EtxB) conjugated to OVA peptide (EtxB-peptide) to address the impact on induction of specific CD8(+) T cells in vivo. Although incubation of DCs with these EtxB-peptide conjugates as such did not induce DC maturation in vitro MHC class I antigen presentation was much more efficient as compared to peptide alone. Antigen presentation was further enhanced upon DC maturation with the TLR-4 ligand LPS. Injection of matured DCs incubated with EtxB-peptide conjugates lead to strong induction of OVA-specific CD8(+) T lymphocytes and fully prevented the outgrowth of lethal B16 melanoma in wild type mice. Our data demonstrate that bacterial non-toxic B subunit-peptide conjugates are potent vaccine vehicles for induction of protective CD8(+) T cell responses.
Fu
Nathalie
N
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
Khan
Selina
S
Quinten
Edwin
E
de Graaf
Natascha
N
Pemberton
Alex J
AJ
Rivett
A Jennifer
AJ
Melief
Cornelis J M
CJ
Ossendorp
Ferry
F
D000818:Animals; D017951:Antigen Presentation; D001427:Bacterial Toxins / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology*; D004768:Enterotoxins / Q000276:immunology*; D029968:Escherichia coli Proteins / Q000276:immunology*; D005260:Female; D005805:Genes, MHC Class I; D008213:Lymphocyte Activation; D008546:Melanoma, Experimental / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL
D001427:Bacterial Toxins; D019496:Cancer Vaccines; D004768:Enterotoxins; D029968:Escherichia coli Proteins; C027538:heat-labile enterotoxin, E coli