Fig. 1. Photo-cleavable TAP inhibitor ICP47 in MHC I antigen presentation pathway. (a) The transporter associated with antigen processing (TAP1/2) translocates proteasomal degradation products from the cytosol into the ER lumen. Peptide loading of MHC I molecules is orchestrated by the peptide-loading complex (PLC), composed of TAP, the chaperone tapasin, the disulfide-reductase ERp57, the lectin calreticulin, the MHC I heavy chain, and β2-microglobulin. Upon successful loading, editing, and proof-reading, stable peptide/MHC I complexes are released and transported to the cell surface to present their antigenic cargo to cytotoxic T-lymphocytes. Antigen processing can be blocked by the TAP inhibitor ICP47 derived from the herpes simplex virus. (b) Photo-conditional ICP47 (pc-ICP47) blocks peptide translocation into the ER lumen. Photolysis induces fragmentation of the pc-ICP47 and subsequently reactivates TAP.
