A Lysosome-Targeted Tetrazine for Organelle-Specific Click-to-Release Chemistry in Antigen Presenting Cells
Nina A. M. Ligthart, Mark A. R. de Geus, Merel A. T. van de Plassche, Diana Torres‐García, Marjolein M. E. Isendoorn, Luuk Reinalda, Daniëlle Ofman, Tyrza van Leeuwen, Sander I. van Kasteren
Abstract
High Resolution Image Download MS PowerPoint Slide Bioorthogonal deprotections are readily used to control biological function in a cell-specific manner. To further improve the spatial resolution of these reactions, we here present a lysosome-targeted tetrazine for an organelle-specific deprotection reaction. We show that trans -cyclooctene deprotection with this reagent can be used to control the biological activity of ligands for invariant natural killer T cells in the lysosome to shed light on the processing pathway in antigen presenting cells. We then use the lysosome-targeted tetrazine to show that long peptide antigens used for CD8 + T cell activation do not pass through this organelle, suggesting a role for the earlier endosomal compartments for their processing.