CD74 molecule (HLA class II antigen-associated invariant chain) (CD74)

CD74, also known as the HLA class II antigen-associated invariant chain (Ii), is a non-polymorphic type II transmembrane glycoprotein that plays a central role in the adaptive immune system [1, 2]. Its primary biological function is acting as a chaperone for MHC class II molecules, ensuring their proper folding and directing their transport from the endoplasmic reticulum to endosomal compartments while preventing premature peptide binding [1, 3]. Beyond its role in antigen presentation, CD74 serves as the high-affinity cell surface receptor for Macrophage Migration Inhibitory Factor (MIF), a pro-inflammatory cytokine that triggers pro-survival and proliferative signaling pathways, including the ERK1/2 and PI3K/AKT cascades [4]. In oncology, CD74 is significantly overexpressed in various hematological malignancies, such as multiple myeloma and B-cell lymphomas, as well as in several solid tumors, while maintaining restricted expression in normal tissues [3, 5]. Because CD74 undergoes rapid internalization upon antibody binding, it is an ideal target for antibody-drug conjugates (ADCs) designed to deliver potent cytotoxic agents directly into malignant cells [5]. Therapeutic strategies currently focus on utilizing monoclonal antibodies like Milatuzumab to induce apoptosis or deliver payloads to treat refractory cancers [3, 5]. Sources: [1] UniProt Consortium. CD74 - HLA class II antigen-associated invariant chain. UniProtKB - P04233. [2] National Center for Biotechnology Information (NCBI). CD74 molecule [Homo sapiens]. Gene ID: 972. [3] Borghese, F., & Clanchy, F. I. (2011). CD74: an emerging opportunity as a therapeutic target in cancer and autoimmune disease. Expert Opinion on Therapeutic Targets. [4] Leng, L., et al. (2003). MIF signal transduction initiated by binding to CD74. Journal of Experimental Medicine. [5] Stein, R., et al. (2007). CD74: a new candidate target for the immunotherapy of B-cell neoplasms. Clinical Cancer Research.

Other names

HLA-DR antigens-associated invariant chainIip33DHLAGMIF receptorCLIP

Antibody-drug conjugate (ADC) mediated cytotoxicity via rapid internalization and lysosomal payload release; Monoclonal antibody-induced apoptosis; Blockade of MIF-CD74 pro-survival signaling axis.