Artikel
The synthetic TLR2 agonist BPPcysMPEG leads to efficient cross-priming against co-administered and linked antigens
Der synthetische TLR2-Agonist BPPcysMPEG induziert eine effektive Immunität zytotoxischer Lymphozyten gegen gleichzeitig verabreichte oder gekoppelte Antigene
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Veröffentlicht: | 2. Juni 2010 |
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Gliederung
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The property of dendritic cells (DC) to generate effective cytotoxic T lymphocyte (CTL) responses is influenced by Toll-like Receptor (TLR) signalling. TLR ligands contain molecular signatures associated with pathogens, are being exploited as potential adjuvants, and have impact on the antigen processing and presentation by DC. We hypothesized that the TLR2/6 heterodimer agonist S-[2,3-bispalmitoyiloxy-(2R)-propyl]-R-cysteinyl-amido-monomethoxyl polyethylene glycol (BPP), a synthetic derivative of the Mycoplasma macrophage activating lipopeptide (MALP-2), is a potent adjuvant for cross-priming against cellular antigens. Systemic administration of BPP induced maturation of CD8α+DC and CD8α+DC in the spleen and resulted in enhanced cross-presentation of intravenously co-administered antigen in mice. In addition, administration of BPP and cell-associated OVA generated an effective CTL response against OVA in vivo in a CD4 T helper cell-dependent manner, but independent of IFN-α. Delivering antigenic peptides directly linked to BPP led to superior CTL immunity as compared to giving antigens and adjuvants admixed. In contrast to other TLR ligands, such as CpG, systemic activation of DC with BPP did not result in shut-down of antigen presentation by splenic DC subsets, although cross-priming against subsequently encountered antigens was reduced. Together our data provide evidence that BPP is a potent stimulus to generate CTL via cross-priming.