Tolerogenic Dendritic Cells on Transplantation: Immunotherapy Based on Second Signal Blockage

Figure 3

Hypothetical mechanism of action of CTLA4-KDEL fusion protein. Transport of proteins between the ER and Golgi apparatus is mediated by two membrane coat complexes, COPI and COPII. COPII mediates ER-to-Golgi transport and COPI mediates retrograde transport. KDEL receptor undergoes retrograde transport only after it binds its ligand [147]. On CTLA4-KDEL transfected cells, the KDEL peptide retains/retrieves proteins to the ER. CTLA4 fused to KDEL is confined to the ER where it binds CD80/86, preventing the passage of these molecules to the cell surface. CD80/CD86 molecules seem to be removed by proteasome-mediated degradation. GC: complex of Golgi; N: nucleus; ER: endoplasmatic reticulum; CTLA4-KDEL: gene construct encoding a modified CTLA4 molecule; COP: cytosolic protein coat complex.