Major histocompatibility complex class II invariant chain (CD74)

The **Major histocompatibility complex class II invariant chain (CD74)** is a single-spanning transmembrane type II membrane glycoprotein that acts as a chaperone required for proper assembly, trafficking, and peptide loading of MHC class II molecules. During biosynthesis in the endoplasmic reticulum, the invariant chain binds to the peptide-binding groove of newly synthesized MHC class II α and β heterodimers, preventing premature peptide loading and stabilizing their conformation[1][2]. It also directs the MHC class II complex into the endocytic pathway, where the invariant chain is sequentially degraded by lysosomal proteases, leaving a peptide fragment (CLIP) in the groove until it is exchanged for an antigenic peptide, typically with the help of HLA-DM[1][2]. CD74 is best known for its role in **adaptive immune responses**, where efficient antigen presentation to CD4+ T lymphocytes is vital for immune surveillance and response to pathogens and tumors. CD74 is also overexpressed in some hematological malignancies and is a validated therapeutic target for monoclonal antibodies such as milatuzumab. Impairment or dysregulation of CD74 function has been implicated in various autoimmune, neoplastic, and infectious disease contexts[1][2].

Other names

Invariant chainCD74IiHLA-DR-associated invariant chain

Blockade of CD74 to modulate antigen presentation or immune response Antibody-mediated targeting for depletion of CD74-expressing cells