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
thattrans-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.