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. The invariant chain (Abbreviated Ii) is a polypeptide involved in the formation and transport of MHC class II protein. The cell surface form of the invariant chain is known as CD74.
The nascent MHC class II protein in the rough ER has its peptide-binding cleft blocked by the invariant chain (Ii; a trimer) to prevent it from binding cellular peptides or peptides from the endogenous pathway. 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, degraded 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 binds to MHC II, releasing CLIP and allowing other peptides to bind. The stable MHC class-II is then presented on the cell surface.
Riberdy JM, Newcomb JR, Surman MJ, et al. (1992). "HLA-DR molecules from an antigen-processing mutant cell line are associated with invariant chain peptides". Nature360 (6403): 474–7. doi:10.1038/360474a0. PMID1448172.
Koch N, Hämmerling GJ (1986). "Ia-associated invariant chain is fatty acylated before addition of sialic acid". Biochemistry24 (22): 6185–90. doi:10.1021/bi00343a023. PMID3866610.
Claesson L, Peterson PA (1983). "Association of human gamma chain with class II transplantation antigens during intracellular transport". Biochemistry22 (13): 3206–13. doi:10.1021/bi00282a026. PMID6576808.
Brown JH, Jardetzky TS, Gorga JC, et al. (1993). "Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1". Nature364 (6432): 33–9. doi:10.1038/364033a0. PMID8316295.
Naujokas MF, Morin M, Anderson MS, et al. (1993). "The chondroitin sulfate form of invariant chain can enhance stimulation of T cell responses through interaction with CD44". Cell74 (2): 257–68. doi:10.1016/0092-8674(93)90417-O. PMID8343954.