CD74 is a non-polymorphic type II integral membrane protein. It has a short N-terminal cytoplasmic tail of 28 amino acids, followed by a single 24 amino acid transmembrane region and an approximately 150 amino acid lumenal domain.¹The CD74 chain is thought to function mainly as a major histocompatibility complex (MHC) class II chaperone, which promotes endoplasmic reticulum (ER) exit of MHC class II molecules, directs them to endocytic compartments, prevents peptide binding in the ER, and contributes to peptide editing in the MHC class II compartment. Class II MHC and invariant chain expression was believed to be restricted to classical antigen-presenting cells (APC); however, during inflammation, other cell types, including mucosal epithelial cells, have also been reported to express class II MHC molecules.²Experiments that investigate cell-surface CD74 are complicated by the fact that CD74 remains on the cell surface for a very short time. The surface half-life of CD74 was calculated to be fewer than 10 minutes.³CD74 however has also recently been shown to have a role as an accessory-signalling molecule because of its macrophage migration-inhibitory factor (MIF).³The restricted expression of CD74 by normal tissues and its very rapid internalization make CD74 an attractive therapeutic target for both cancer and immunologic diseases.⁴

1.Becker-Herman, S., Arie, G., Medvedovsky, H., et al.CD74 is a member of the regulated intramembrane proteolysis-processed protein familyMol. Biol. Cell16(11)5061-5069(2005) 2.Barrera, C.A., Beswick, E.J., Sierra, J.C., et al.Polarized expression of CD74 by gastric epithelial cellsJ. Histochem. Cytochem.53(12)1481-1489(2005) 3.Starlets, D., Gore, Y., Binsky, I., et al.Cell-surface CD74 initiates a signaling cascade leading to cell proliferation and survivalBlood107(12)4807-4816(2006) 4.Burton, J.D., Ely, S., Reddy, P.K., et al.CD74 is expressed by multiple myeloma and is a promising target for therapyClin. Cancer Res.10(19)6606-6611(2004)