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The use of synthetic long peptides (SLP) has been proven to be a promising approach to induce adaptive immune responses in vaccination strategies. Here, we analyzed whether the efficiency to activate cytotoxic T cells by SLP-based vaccinations can be increased by conjugating SLPs to mannose residues. We could demonstrate that mannosylation of SLPs results in increased internalization by the mannose receptor (MR) on murine antigen-presenting cells. MR-mediated internalization targeted the mannosylated SLPs into early endosomes, from where they were cross-presented very efficiently compared to non-mannosylated SLPs. The influence of SLP mannosylation was specific for cross-presentation, as no influence on MHC II-restricted presentation was observed. Additionally, we showed that vaccination of mice with mannosylated SLPs containing epitopes from either ovalbumin or HPV E7 resulted in enhanced proliferation and activation of antigen-specific CD8 +  T cells. These findings demonstrate that mannosylation of SLPs augments the induction of a cytotoxic T cell response  in vitro  and  in vivo  and might be a promising approach to induce cytotoxic T cell responses in e.g. cancer therapy and anti-viral immunity.

Enhanced Cross-Presentation and Improved CD8+ T Cell Responses after Mannosylation of Synthetic Long Peptides in Mice