Related Experiment Video
Updated: Dec 12, 2025
Ligand Nano-cluster Arrays in a Supported Lipid Bilayer
Published on: April 23, 2017
Targeting of the C-Type Lectin Receptor Langerin Using Bifunctional Mannosylated Antigens
Rui-Jun Eveline Li1, Tim P Hogervorst2, Silvia Achilli3
1Department of Molecular Cell Biology and Immunology, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
Insights
Synthetic mannoside clusters targeting Langerin on skin Langerhans cells (LCs) show increased binding affinity with more mannosides. However, this did not improve antigen presentation for cancer immunotherapy vaccines.
Area of Science:
- Immunology
- Glycobiology
- Cancer Immunotherapy
Background:
- Langerhans cells (LCs) are crucial skin-resident antigen-presenting cells.
- The C-type lectin receptor Langerin (CD207) on LCs is a promising target for cancer immunotherapy vaccines.
- Targeting LCs aims to enhance antigen delivery and T cell responses.
Purpose of the Study:
- To synthesize and evaluate mannoside clusters for binding to Langerin.
- To assess the efficacy of mannoside-targeted conjugates for antigen presentation.
- To investigate the relationship between glycan targeting and T cell activation in cancer vaccines.
Main Methods:
- Synthesis of 20 mannoside clusters with varying mannoside numbers (mono-, di-, tri-) on an oligopeptide backbone.
- Surface plasmon resonance and flow cytometry to quantify Langerin binding affinity.
- Development of bifunctional conjugates linking mannoside clusters to a model melanoma antigen (gp100 peptide).
- Assessment of antigen uptake by LCs and subsequent antigen presentation to T cells.
Main Results:
- Langerin binding affinity increased with the number of mannoside units in the clusters.
- Hexavalent mannoside clusters exhibited binding affinities between 3-12 μM.
- Bifunctional conjugates were internalized by LCs in a Langerin-dependent manner.
- Despite efficient uptake, limited antigen presentation to cytotoxic T cells was observed.
Conclusions:
- Mannoside cluster density positively correlates with Langerin binding affinity.
- Langerin-mediated uptake does not guarantee enhanced antigen presentation for effective T cell responses.
- Future immunotherapeutic vaccine design must consider both target binding and biological function, including antigen presentation.
Abstract:
Langerhans cells (LCs) are antigen-presenting cells that reside in the skin. They uniquely express high levels of the C-type lectin receptor Langerin (CD207), which is an attractive target for antigen delivery in immunotherapeutic vaccination strategies against cancer. We here assess a library of 20 synthetic, well-defined mannoside clusters, built up from one, two, and three of six monomannosides, dimannosides, or trimannosides, appended to an oligopeptide backbone, for binding with Langerin using surface plasmon resonance and flow cytometric quantification. It is found that Langerin binding affinity increases with increasing number of mannosides. Hexavalent presentation of the mannosides resulted in binding affinities ranging from 3 to 12 μM. Trivalent presentation of the dimannosides and trimannosides led to Langerin affinity in the same range. The model melanoma gp100 antigenic peptide was subsequently equipped with a hexavalent cluster of the dimannosides and trimannosides as targeting moieties. Surprisingly, although the bifunctional conjugates were taken up in LCs in a Langerin-dependent manner, limited antigen presentation to cytotoxic T cells was observed. These results indicate that targeting glycan moieties on immunotherapeutic vaccines should not only be validated for target binding, but also on the continued effects on biology, such as antigen presentation to both CD8+ and CD4+ T cells.
