Disease relevance of CD74

• Helicobacter pylori binds to CD74 on gastric epithelial cells and stimulates interleukin-8 production [1].
• Inhibition of Macrophage Migration Inhibitory Factor or Its Receptor (CD74) Attenuates Growth and Invasion of DU-145 Prostate Cancer Cells [2].
• CD74 is expressed by multiple myeloma and is a promising target for therapy [3].
• The fate of antibody (Ab) LL1, which reacts with the invariant chain (Ii) subunit of the immature MHC class-II antigen (CD74) after binding to the surface of B-cell lymphomas was investigated [4].
• LN-2 (CD74). A marker to distinguish atypical fibroxanthoma from malignant fibrous histiocytoma [5].

High impact information on CD74

• These data establish CD44 as an integral member of the CD74 receptor complex leading to MIF signal transduction [6].
• Using expression cloning and functional analysis, we report herein that CD74, a Type II transmembrane protein, is a high-affinity binding protein for MIF [7].
• Alternative splicing and alternative initiation of translation explain the four forms of the Ia antigen-associated invariant chain [8].
• The second group consists of genes that are expressed in phagocytes such as caveolin-1 and CD74 [9].
• Cell-surface CD74 initiates a signaling cascade leading to cell proliferation and survival [10].

Chemical compound and disease context of CD74

• Thus, blocking MIF either at the ligand (MIF) or receptor (CD74) may provide new, targeted specific therapies for androgen-independent prostate cancer [2].
• We examined formalin-fixed placentas from four cases of confirmed congenital cytomegalovirus infection using an in situ DNA probe to cytomegalovirus, and a variety of antibodies to leukocyte antigens, including anti-CD68, CD45RO, CDw75, CD74, IgG, IgM, and IgA [11].

Biological context of CD74

• This study investigated the interaction of H. pylori with the class II major histocompatibility complex (MHC)-associated invariant chain (Ii; CD74), which was found to be highly expressed by gastric epithelial cells [1].
• The binding of H. pylori to CD74 presents a novel insight into an initial interaction of H. pylori with the gastric epithelium that leads to upregulation of inflammatory responses [1].
• MIF signal transduction initiated by binding to CD74 [7].
• Therefore, we hypothesized that increased expression or surface localization of CD74 and MIF overexpression by prostate cancer cells regulated tumor cell viability [2].
• PURPOSE: CD74 (HLA-DR-associated invariant chain) plays a role in antigen presentation [3].

Anatomical context of CD74

• We have previously shown that H. pylori binds to CD74 on gastric epithelial cells [12].
• Further confirmation of the interaction of urease B with CD74 was obtained using a fibroblast cell line transfected with CD74 that also responded with NF-kappaB activation and IL-8 production [12].
• Macrophages with positive staining for the antimicrobial peptides also stained positively for CD68 and CD74 [13].
• CD74 expression was increased dramatically on gastric biopsies from H. pylori-positive patients and gastric cell lines exposed to the bacteria [14].
• Schwann cells in biopsies from patients and normal controls expressed high levels of the invariant chain, CD74, a molecule involved in the intracellular sorting of MHC class II molecules [15].

Associations of CD74 with chemical compounds

• Formalin-fixed, paraffin-embedded multi-organ tissue blocks from aborted fetuses (age range 7-22 weeks) were immunostained for Ii/CD74 and MHC class II antigens using commercially available monoclonal antibodies for Ii/CD74 (LN2) and MHC class II antigens (LN3), respectively [16].
• MIF binding was associated with the serine phosphorylation of CD74 and CD44 [6].
• EXPERIMENTAL DESIGN: Doxorubicin (dox) conjugates of the murine and humanized versions of the anti B-cell antibody LL1, targeting CD74, were prepared, along with a nonspecific control dox-antibody conjugate, targeting carcinoembryonic antigen [17].
• The subcellular distribution patterns of molecules involved in the process of antigen loading [HLA-DR, HLA-DM, and the cytoplasmic and luminal parts of the invariant chain (Ii, CD74)] were investigated in Langerhans cells (LC), both qualitatively and quantitatively [18].
• Methods for correction of chromatic aberration and identification of submicroscopic artefacts are presented, with data for the lipopolysaccharide/CD14 and MHC class II/CD74 systems [19].

Physical interactions of CD74

• MIF appears to interact with cell surface CD74, with consequent activation of MAP kinases but possibly not NFkappaB intracellular signal transduction [20].

Other interactions of CD74

• Increased CD74 expression by cells increased IL-8 production in response to H. pylori, and agents that block CD74 decreased these responses [1].
• These cells were CD20+, CD3-, CD45RO-, KP-1-, PGM1-, with occasional positive reaction for MB-1 and CD74, indicating their B-cell nature, i.e., MBL [21].
• Our evidence suggests MIF interacts with the invariant chain, CD74 and the major cell surface receptor for HA, CD44 [22].
• Neoplastic lymphoid cells were positive for CD20, CD45, CD74 and CDw75 [23].
• A panel of monoclonal antibodies (Leucocyte Common Antigen [CD45], LN-1 [CDw75], LN-2 [CD74], LN-3, L-26, UCHL-1 [CD45RO] and MT-1) which identify B and T cell surface markers were applied to benign lymphocytoma cutis and malignant lymphoma of the skin in paraffin-embedded sections [24].

Analytical, diagnostic and therapeutic context of CD74

• Recombinant urease B was found to bind directly to CD74 in immunoprecipitation and flow cytometry studies [12].
• EXPERIMENTAL DESIGN: CD74 expression was assessed by immunohistochemistry in bone marrow biopsies of known multiple myeloma cases [3].
• SDS-PAGE analysis of plasma samples with high sCD74 concentrations (>3.0 relative units) revealed four isoforms of sCD74 with molecular weights of 45, 43, 35, 31 kDa corresponding to known sizes of intracellular CD74 [25].
• It was revealed by immunofluorescence, confocal microscopy, and subcellular fractionation techniques that human trophoblasts, although not expressing any surface HLA-DR antigens, constitutively express intracellular HLA-DR, HLA-DO, and CD74, but not HLA-DM [26].
• Localization of an antibody to CD74 (MHC class II invariant chain) to human B cell lymphoma xenografts in nude mice [27].

References