Cluster of differentiation 74 (CD74) is an important integral membrane protein that serves as a chaperone for MHC class II molecules. CD74, also known as the invariant chain or Ii, is needed for the proper folding and trafficking of MHC class II in antigen presenting cells. CD74 serves as a scaffold for MHC class II assembly. During assembly CD74 blocks the peptide binding cleft of MHC class II to prevent binding of antigenic peptides. Following endocytosis of antigen the CD74-MHC class II complex is trafficked to the endosome where CD74 is digested leaving only the 9 amino acid CLIP peptide in the binding cleft. CLIP peptide can then be released to allow the binding of antigenic peptide and the trafficking of the antigen bound MHC molecules to the plasma membrane. CD74 also plays important roles in various cell signaling pathways including the activation of nuclear factor-kB during B-cell maturation. CD74's function in B-cell proliferation and survival make it a potential target in the treatment of B-cell malignancies.
In order to examine the mechanism of MHC class II maturation, Denzin et al. used a CD74 antibody targeted to the CLIP peptide to affinity purify interacting proteins (1). This technique allowed the researchers to characterize intermediate protein complexes during antigen processing. Researchers from the Mount Sinai School of Medicine identified candidate genes involved in immune and inflammatory responses that are correlated with dementia in elderly patients (2). They used the CD74 antibody among others to examine the levels of these candidate proteins by western blot. This led to the characterization of an alternative signature for dementia separate from that seen in Alzheimer’s disease. The Skov group at the University of Copenhagen identified an important role for CD74 in the transport and processing of ULBP2, an important prognostic marker in several cancers (3). The researchers used siRNA to deplete CD74 and confirmed knockdown through western blots with the CD74 antibody. These experiments demonstrated the function of CD74 and the endosomal transport pathway in ULBP2 processing in cancer cells. Zheng et al. used the CD74 antibody for immunohistochemistry in their analysis of gastric cancer specimens (4). They showed CD74 along with MIF and TLR4 are overexpressed and offer potential targets for treatments strategies. Similarly the Gajda group used the CD74 antibody to examine gliomas by immunofluorescence (5). Their study showed CD74 localization not only to tumor cells but also to infiltrating macrophages suggesting a role in evasion of the immune system.
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