Cell
Volume 63, Issue 4, 16 November 1990, Pages 707-716
Journal home page for Cell

Article
MHC class II-associated invariant chain contains a sorting signal for endosomal compartments

https://doi.org/10.1016/0092-8674(90)90137-4Get rights and content

Abstract

The invariant chain (Ii) is a transmembrane protein that associates with the MHC class II molecules in the endoplasmic reticulum. Expression of II in MHC class II-negative CV1 cells showed that it acquired complex-type oligosaccharide side chains and was retained in endosomal compartments. To search for a sorting signal, we made progressive deletions from the cytoplasmic N-terminus of Ii. Deleting 11 amino acid residues resulted in a protein that was still sorted and retained in endosomal vesicles, whereas deletion of 15 or more amino acid residues resulted in a protein that became resident in the plasma membrane. Amino acids 12–15 are thus essential for intracellular transport to endosomal compartments. As Ii is intracellularly associated with the MHC class II molecules, it is proposed that II determines the intracellular transport route of these molecules.

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      A recent study using mice that lack specific promoter regions of the CIITA gene showed that sMHC II molecules are mainly released from dendritic cells and macrophages but not from B cells [12]. Ii is essential in antigen presentation by transporting MHC II molecules to the endosomal/lysosomal compartment [14,15]. Moreover, Ii p41, but not the p31 isoform, associates with cathepsin L to stabilize their mature form and protects cathepsin L from degradation by other proteases [30,31].

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