HLA class II histocompatibility antigen gamma chain also known as HLA-DR antigens-associated invariant chain or CD74 (Cluster of Differentiation 74), is a protein that in humans is encoded by the CD74gene.[1][2] The invariant chain (Abbreviated Ii) is a polypeptide involved in the formation and transport of MHC class II protein.[3] The cell surface form of the invariant chain is known as CD74.
The nascent MHC class II protein in the rough ER binds a segment of the invariant chain (Ii; a trimer) in order to shape the peptide binding groove and prevent formation of a closed conformation. Binding to Ii might also prevent binding of peptides from the endogenous pathway to the groove of MHC class II. The invariant chain also facilitates MHC class II's export from the ER in a vesicle. The signal for endosomal targeting resides in the cytoplasmic tail of the invariant chain. This fuses with a late endosome containing the endocytosed proteins. It is then cleaved by cathepsin S (cathepsin L in cortical thymic epithelial cells), leaving only a small fragment called CLIP which blocks peptide binding until HLA-DM interacts with MHC II, releasing CLIP and allowing other peptides to bind. The stable MHC class-II is then presented on the cell surface.
Clinical significance
Cancer
Found on a number of cancer cell types. Possible cancer therapy target. See Milatuzumab#CD74
↑Baerlecken NT, Nothdorft S, Stummvoll GH, Sieper J, Rudwaleit M, Reuter S, Matthias T, Schmidt RE, and Witte T (2014). "Autoantibodies against CD74 in spondyloarthritis". Annals of the Rheumatic Diseases. 73 (6): 1211–14. doi:10.1136/annrheumdis-2012-202208.
↑ Baraliakos X, Baerlecken N, Witte T, Heldmann F, and Braun J (2014). "High prevalence of anti-CD74 antibodies specific for the HLA class II-associated invariant chain peptide (CLIP) in patients with axial spondyloarthritis". Annals of the Rheumatic Diseases. 73 (6): 1079–1082. doi:10.1136/annrheumdis-2012-202177.
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