CD74. also known as invariant chain (Ii), is a transmembrane protein primarily recognized for its role as a chaperone for major histocompatibility complex class II (MHC II) molecules. It facilitates the proper folding, transport, and peptide loading of MHC II in antigen-presenting cells, such as B cells and dendritic cells. Beyond its structural role, CD74 acts as a signaling receptor for macrophage migration inhibitory factor (MIF), a cytokine involved in inflammation, cell survival, and immune regulation. This interaction activates pathways like NF-κB and MAPK, influencing processes such as apoptosis, proliferation, and inflammatory responses.
CD74 is overexpressed in various B-cell malignancies (e.g., lymphoma, leukemia) and autoimmune disorders (e.g., rheumatoid arthritis), making it a therapeutic target. Antibodies targeting CD74 are designed to block its interactions with MIF or disrupt MHC II-mediated antigen presentation. These antibodies are utilized in research to study immune regulation and in diagnostics to detect CD74 expression in pathological tissues. Therapeutically, anti-CD74 antibodies like milatuzumab have been explored in clinical trials for hematologic cancers, leveraging their potential to induce antibody-dependent cellular cytotoxicity (ADCC) or deliver cytotoxic payloads. Challenges include optimizing specificity and minimizing off-target effects. Overall, CD74 antibodies represent a promising tool for both understanding immune mechanisms and developing targeted therapies.