Dissertation

Spatio-temporal aspects of antigen cross-presentation in dendritic cells: with click-to-release chemistry

The first steps are made in personalised cancer vaccination strategies, which aim to induce a more specific immune response with fewer side effects. The activation of cytotoxic T cells is crucial for an effective immune response.

Author

N.A.M. Ligthart

Date

12 September 2024

Links

Thesis in Leiden Repository

In this thesis, the cellular processes behind antigen cross-presentation (signal 1) are further researched. For this, we make use of the bioorthogonal ‘click-to-release’ strategy to shield glycolipid and peptide antigens. A strategically placed, small chemical group, trans-cyclooctene (TCO), is used to minimise interference on processing, however, effectively blocks T cell activation. The chemical protecting group can be selectively removed by introducing a tetrazine, serving as a deprotection compound. The tetrazine clicks onto the protecting TCO group, inducing the release of the entire tetrazine-TCO complex. This click-to-release approach allows for precise regulation of T cell activation. Consequently, T cell activation assays can be used to research antigen cross-presentation, in both a spatially and temporally manner.

• antigen presentation
• click chemistry
• dendritic cells