HLA class II histocompatibility antigen gamma chain (CD74) (CD74)

HLA class II histocompatibility antigen gamma chain (CD74), also known as the invariant chain or MHC class II invariant chain, is a type II transmembrane glycoprotein that serves as a molecular chaperone for MHC class II molecules, facilitating their proper folding, trafficking from the endoplasmic reticulum to endosomal compartments, and antigen peptide loading for CD4+ T cell responses.[3][4][6] On the cell surface, CD74 acts as a receptor for macrophage migration inhibitory factor (MIF), triggering signaling cascades including ERK, PI3K-Akt, MAPK, and NF-κB pathways that promote cell survival, proliferation, chemotaxis, and innate immune responses, often in complex with CD44.[1][3][5][6] Expressed primarily in antigen-presenting cells like B cells, dendritic cells, and microglia, CD74 is upregulated in reactive microglia during neurodegenerative diseases such as Alzheimer's and multiple sclerosis, as well as in cancers like triple-negative breast cancer and melanoma, where it contributes to tumor progression and immunosuppression.[1][2] In cardiovascular contexts, it influences atherosclerosis via adaptive immunity modulation.[6] While CD74 holds promise as a therapeutic target for MIF-CD74 blockade in inflammation-driven diseases and cancer, challenges include potential disruption of antigen presentation and risks of altering immune homeostasis.[1][2][6] Isoforms (e.g., p33, p41 in humans) add complexity to its functions in different tissues.[1][2]

Other names

invariant chainMHC class II invariant chainHLA-DR antigens-associated invariant chainIileukocyte differentiation antigen 74

Receptor for macrophage migration inhibitory factor (MIF) leading to activation of ERK, PI3K, NF-κB, MAPK, and Akt pathways; chaperone for MHC class II folding and trafficking; forms complex with CD44 to initiate oncogenic signaling