Endosomal aspartic proteinases are required for invariant-chain processing

Maja A. Marić, Michael D. Taylor, Janice Blum

Research output: Contribution to journalArticle

164 Citations (Scopus)

Abstract

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 languageEnglish (US)
Pages (from-to)2171-2175
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number6
StatePublished - Mar 15 1994
Externally publishedYes

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Aspartic Acid Proteases
Peptides
Peptide Hydrolases
Cysteine Proteinase Inhibitors
Histocompatibility
Cysteine Proteases
Endosomes
Antigen-Presenting Cells
Surface Antigens
invariant chain
Glycoproteins
Cell Line
Enzymes

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Endosomal aspartic proteinases are required for invariant-chain processing. / Marić, Maja A.; Taylor, Michael D.; Blum, Janice.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 6, 15.03.1994, p. 2171-2175.

Research output: Contribution to journalArticle

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