A lysosome-targeted tetrazine for organelle-specific click-to-release chemistry in antigen presenting cells

Abstract

Bioorthogonal deprotectionsare readily used to control biologicalfunction in a cell-specific manner. To further improve the spatialresolution of these reactions, we here present a lysosome-targetedtetrazine for an organelle-specific deprotection reaction. We showthat trans-cyclooctene deprotection with this reagentcan be used to control the biological activity of ligands for invariantnatural killer T cells in the lysosome to shed light on the processingpathway in antigen presenting cells. We then use the lysosome-targetedtetrazine to show that long peptide antigens used for CD8(+) T cell activation do not pass through this organelle, suggestinga role for the earlier endosomal compartments for their processing.