Immunogenic peptides are displayed in the context of class II histocompatibility proteins on the surface of antigen-presenting cells. Class II α and β subunits bind the invariant chain (I-chain), a transmembrane glycoprotein which must dissociate prior to peptide presentation. Proteolytic release of I-chain in an acidic compartment is followed by class II αβ surface expression. Two distinct proteinases sequentially catalyze I-chain dissociation in B-lymphoblastoid cell lines. An aspartic proteinase initiates processing whereas a cysteine proteinase catalyzes the final stages of I- chain release. Inactivation of these enzymes prevents class II αβ maturation, demonstrating that acidic proteinases are essential for the generation of functional class II complexes. I-chain processing was localized to a dense endosomal compartment, suggesting this is the first site where class II αβ become accessible to peptides: I-chain fragments complexed with class II αβ accumulate in dense endosomes of B-lymphoblastoid cells treated with cysteine proteinase inhibitors. A signal for endosomal retention/targeting present in the cytoplasmic tail of these fragments may sequester class II αβ in this compartment until I-chain processing is complete.
|Original language||English (US)|
|Number of pages||5|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - Mar 15 1994|
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