Figure 1

CNS-targeting receptor and FoxP3 translation and function. (A) The CARαMOG-FoxP3 vector contains a scFv cloned from the 8.18 C5 hybridoma. The scFv is linked via an antibody hinge region to the transmembrane and intracellular part of a CD3 zeta chain. The zeta chain is further fused to an intracellular CD28 domain. The murine FoxP3 gene was inserted into the construct after a 2A peptide sequence. Upon translation, the whole expression cassette is translated into a CARFoxP3 fusion protein that is self-cleaved at the 2A site to produce the two separate proteins CARαMOG and FoxP3. (B) CARαMOG and FoxP3 is transported to the cell surface and nucleus, respectively. At the cell surface CARαMOG can bind to MOG + cells to attach the Treg to those cells and prevent immune attacks on MOG + cells such as oligodendrocytes in the CNS. FoxP3 will drive the Treg phenotype by regulating gene transcription in the nucleus.