Leiden University Scholarly Publications

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Steuten, K. (2026)

On the interactions between carbohydrates and immune cells

Doctoral Thesis
The immune system relies on carbohydrates, both as signalling molecules and as energy source. Yet the precise molecular interactions and pathways underlying these processes remain poorly understood. This thesis develops and applies two quantitative methods to study carbohydrate–immune cell interactions in physiological settings.
The first method, Glyco-PAINT, is a super-resolution microscopy approach in which fluorescently labelled glycan ligands transiently bind their lectin receptors on live cells, generating single-molecule binding events that encode kinetic parameters. Chapter 2 describes an automated processing pipeline that makes the technique compatible with heterogeneous primary immune cells. Chapters 3 and 4 apply this tool to study the binding of mannose-modified peptide vaccines and sialic acid ligands to dendritic cells and macrophages. These studies reveal unexpected inverse correlations between mannose binding and antigen cross-presentation,...Show moreThe immune system relies on carbohydrates, both as signalling molecules and as energy source. Yet the precise molecular interactions and pathways underlying these processes remain poorly understood. This thesis develops and applies two quantitative methods to study carbohydrate–immune cell interactions in physiological settings.
The first method, Glyco-PAINT, is a super-resolution microscopy approach in which fluorescently labelled glycan ligands transiently bind their lectin receptors on live cells, generating single-molecule binding events that encode kinetic parameters. Chapter 2 describes an automated processing pipeline that makes the technique compatible with heterogeneous primary immune cells. Chapters 3 and 4 apply this tool to study the binding of mannose-modified peptide vaccines and sialic acid ligands to dendritic cells and macrophages. These studies reveal unexpected inverse correlations between mannose binding and antigen cross-presentation, and demonstrate that removal of cis-ligands from the macrophage surface enhances sialic acid ligand binding.
The second method, developed in Chapter 5, identifies a novel bioorthogonal glucose analog, 6-DAG, to map nutrient uptake in cancer and immune cells in a mouse tumor model. Application of the method provides crucial insights into the competitive nutrient uptake dynamics between cancer and immune cells in the tumor microenvironment. Together, these tools provide a new quantitative framework for understanding the role of carbohydrates in immune regulation.Show less
Carbohydrates
Immune Cells
Glycobiology
Superresolution Microscopy
Glucose
Glutamine
Tumor Microenvironment
All authors
Steuten, K.
Supervisor
Kasteren, S.I. van; Bonger, K.M.
Committee
Ubbink, M.; Codee, J.D.C.; Le Dévédec, S.E.; Albertazzi, L.; Ossendorp, F.A.
Qualification
Doctor (dr.)
Awarding Institution
Leiden Institute of Chemistry (LIC), Faculty of Science, Leiden University
Date
2026-07-02

Funding

Sponsorship
ZonMW; De Nederlandse Vereniging voor Microscopie