CD74 Specific Neutra™ Antibody Products

Cluster of Differentiation 74 (CD74, aliases DHLAG, CLIP, HLADG, etc., also known as invariant chain (Ii), ) is a type II transmembrane protein dominantly distributed on APCs. It is recognized as a molecular chaperone of MHC II molecules and is closely involved in antigen presentation. CD74 is composed of a transmembrane region, a N-terminal cytoplasmic region, and a C-terminal extracellular region. In humans, there are four CD74 isoforms divided by molecular weight, p33, p35, p41, and p43, among which p33 (~33 kDa, 216 aa) is the most common isoform.

Its Gene ID: 972, UniProtKB ID: P04233, and OMIM ID: 142790.

CD74 Functions and Signaling Pathways

CD74 is initially identified to participate in exogenous antigen presentation with MHC II molecules, occupying the binding groove of MHC II. More recent studies have revealed that it also partakes in the endogenous presentation of antigens through MHC I molecules. Besides, along with CXCR2, CXCR4, and CD44, CD74 also acts as a membrane receptor of MIF and D-DT/MIF2 with high affinity, responsible for the activation of several pathophysiological pathways, including PI3K/Akt, AMPK, NF-κB, and ERK pathways, thus regulating the differentiation, maturation, cell proliferation, and metabolism of B cells in a variety of diseases, e.g. ischemic heart disease, hepatic fibrosis, atherosclerosis, immune disorders, pathological myocardial hypertrophy, and tumors.

Fig.1 Primary functions of leukocyte CD74.¹

In cardiovascular diseases, MIF suppresses JNK signaling and triggers ERK1/2-mediated cardiomyocyte apoptosis to exert myocardial protection. MIF/CD74 and MIF2/CD74 can improve the uptake of glucose and utilization by activating AMPK signaling to promote the expression of GLUT4 and inhibit fatty acid oxidation by inhibiting ACC.

Fig.2 Signaling cascades in cardiovascular diseases involving MIF/CD74 and MIF2/CD74.¹

Besides, MIF/CD74 stimulates a signaling cascade that leads to the release of its cytosolic intracellular domain (CD74-ICD), which exerts transcriptional regulation in chronic lymphocytic leukemia (CLL) cells, then forming complexes in the cytosol with transcription factors, like PAX5, and binding the chromatin at more sites compared with those in CLL cells. CD74-ICD-PAX5 complex binds to the promoters of a DMTF1, a tumor-suppressor gene, to negatively regulate its expression at the transcriptional level.

Antibodies Targeting CD74

CD74 possesses rapid endocytosis properties, and its expression levels 4 are observed to be elevated in a wide range of tumor cells, making it a promising therapeutic target for research and clinical purposes. There has been a monoclonal antibody (mAb) targeting CD74 approved to be used widely in the therapy of several tumors, including various lymphomas and chronic granulocytic leukemia, as well as autoimmune diseases like SL. It inhibits the adhesion molecules β7-integrin and CD62L, subsequently inhibiting the proliferation of B-cells. Antibodies targeting CD74 also serve as robust research tools in many projects.

Creative Biolabs offers several different anti-CD74 antibody products. These antibodies are recombinantly expressed and could be used for various purposes. Customization of CD74-based neutralizing antibodies is also available for you here.

REFERENCE

1. Li, Qiu-Lin, et al. "The role of CD74 in cardiovascular disease." Frontiers in Cardiovascular Medicine 9 (2023): 1049143. Under open access license CC BY 4.0, without modification.