Endosomal aspartic proteinases are required for invariant-chain processing.

AUTOR(ES)

Marić, M A

RESUMO

Immunogenic peptides are displayed in the context of class II histocompatibility proteins on the surface of antigen-presenting cells. Class II alpha and beta 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 alpha beta 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 alpha beta 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 alpha beta become accessible to peptides. I-chain fragments complexed with class II alpha beta 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 alpha beta in this compartment until I-chain processing is complete.

Documentos Relacionados

• Binding of an invariant-chain peptide, CLIP, to I-A major histocompatibility complex class II molecules.
• Identification of the glycosaminoglycan-attachment site of mouse invariant-chain proteoglycan core protein by site-directed mutagenesis.
• A promoterless retroviral vector indicates that there are sequences in U3 required for 3' RNA processing.
• Proteasomes are regulated by interferon gamma: implications for antigen processing.
• Multiple N-ethylmaleimide-sensitive components are required for endosomal vesicle fusion.