Bioorthogonal Cleavage and Exchange of Major Histocompatibility Complex Ligands by Employing Azobenzene-Containing Peptides

Bioorthogonal cleavable linkers are attractive building blocks for compounds that can be manipulated to study biological and cellular processes. Sodium dithionite sensitive azobenzene‐containing (Abc) peptides were applied for the temporary stabilization of recombinant MHC complexes, which can then be employed to generate libraries of MHC tetramers after exchange with a novel epitope. This technology represents an important tool for high‐throughput studies of disease‐specific T cell responses. As easy as Abc: Replacement of an azobenzene‐containing (Abc) peptide with novel MHC ligands can be triggered by sodium dithionite. The Abc peptide (turquoise) is cleaved into two fragments, which are released from the binding groove. A novel epitope (orange) can then reoccupy the protein complex. This strategy enables the parallel generation of an array of MHCs with novel antigen‐specificities for use in high‐throughput studies of T cell responses.