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The final N-terminal trimming of a subaminoterminal proline-containing HLA class I-restricted antigenic peptide in the cytosol is mediated by two peptidases
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2002 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 169, no 8, 4161-4171 p.Article in journal (Refereed) Published
Abstract [en]

The proteasome produces MHC class I-restricted antigenic peptides carrying N-terminal extensions, which are trimmed by other peptidases in the cytosol or within the endoplasmic reticulum. In this study, we show that the N-terminal editing of an antigenic peptide with a predicted low TAP affinity can occur in the cytosol. Using proteomics, we identified two cytosolic peptidases, tripeptidyl peptidase II and puromycin-sensitive aminopeptidase, that trimmed the N-terminal extensions of the precursors produced by the proteasome, and led to a transient enrichment of the final antigenic peptide. These peptidases acted either sequentially or redundantly, depending on the extension remaining at the N terminus of the peptides released from the proteasome. Inhibition of these peptidases abolished the CTL-mediated recognition of Ag-expressing cells. Although we observed some proteolytic activity in fractions enriched in endoplasmic reticulum, it could not compensate for the loss of tripeptidyl peptidase II/puromycin-sensitive aminopeptidase activities.

Place, publisher, year, edition, pages
2002. Vol. 169, no 8, 4161-4171 p.
Keyword [en]
Acetylcysteine/*analogs & derivatives/pharmacology, Amino Acid Chloromethyl Ketones/pharmacology, Amino Acid Sequence, Aminopeptidases/antagonists & inhibitors/metabolism, Antigen Presentation/drug effects, Cell Line, Cytosol/enzymology/*immunology/*metabolism, Enzyme Inhibitors/pharmacology, HLA-B Antigens/genetics/immunology/*metabolism, Humans, Hydrolysis, Molecular Sequence Data, Oligopeptides/genetics/immunology/*metabolism, Peptide Fragments/biosynthesis/immunology/*metabolism, Proline/*metabolism, Protein Precursors/metabolism, Protein Processing; Post-Translational/immunology, Puromycin/pharmacology, Serine Endopeptidases/metabolism/*physiology, T-Lymphocytes; Cytotoxic/enzymology/immunology/metabolism, Transfection, Tumor Cells; Cultured
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-10406PubMedID: 12370345OAI: oai:DiVA.org:uu-10406DiVA: diva2:38174
Available from: 2007-03-22 Created: 2007-03-22 Last updated: 2013-11-05Bibliographically approved

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ReferencesLink to record
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