HLA class II antigen-associated invariant chain (CD74) (CD74)

HLA class II antigen-associated invariant chain (CD74) is a non-polymorphic type II transmembrane glycoprotein that plays a critical role as a chaperone for MHC class II molecules [UniProt: P04233]. It ensures the proper folding and transport of MHC II complexes from the endoplasmic reticulum to the endocytic pathway, where it is eventually degraded to allow for peptide loading [PubMed: 10590721]. Beyond its role in antigen presentation, CD74 serves as a high-affinity cell surface receptor for the cytokine Macrophage Migration Inhibitory Factor (MIF), triggering signaling cascades such as the ERK1/2 and AKT pathways that promote cell survival and proliferation [PubMed: 12761501]. CD74 is highly expressed in various hematological malignancies, including multiple myeloma and B-cell lymphomas, as well as certain solid tumors, making it an attractive therapeutic target [PubMed: 22431105]. Targeting CD74 mRNA via shRNA is an experimental approach designed to silence the expression of this protein, thereby inhibiting MIF-mediated pro-survival signaling and impairing the tumor's ability to evade the immune system [PubMed: 18480454]. Other therapeutic strategies include monoclonal antibodies like milatuzumab and antibody-drug conjugates like STRO-001, which aim to induce direct cell death or deliver cytotoxic payloads to CD74-expressing cells [ClinicalTrials.gov].

Other names

IiInvariant chainHLA-DR-associated invariant chainp33MIF receptor

RNA interference (RNAi) mediated by short hairpin RNA (shRNA) leads to the sequence-specific degradation of CD74 mRNA, resulting in the knockdown of CD74 protein expression and subsequent inhibition of MIF-induced survival signaling [PubMed: 18480454].