CD74

CD74, the MHC class II-associated invariant chain (Ii), is a type II transmembrane glycoprotein encoded by a gene on chromosome 5q33. In the endoplasmic reticulum it assembles with MHC class II alpha/beta heterodimers, blocking premature peptide loading and delivering the complexes to endosomal compartments where cleavage leaves the CLIP fragment for exchange. Beyond chaperoning antigen presentation, membrane CD74 acts as a receptor for macrophage migration inhibitory factor (MIF), and proteolytic release of its intracellular domain activates NF-kappaB-dependent transcription. CD74 is constitutively expressed on B cells and antigen-presenting cells, and its high density on malignant B cells in multiple myeloma is exploited by antibodies such as milatuzumab.