Production of an antigenic peptide by insulin-degrading enzyme.

Abstract:

:Most antigenic peptides presented by major histocompatibility complex (MHC) class I molecules are produced by the proteasome. Here we show that a proteasome-independent peptide derived from the human tumor protein MAGE-A3 is produced directly by insulin-degrading enzyme (IDE), a cytosolic metallopeptidase. Cytotoxic T lymphocyte recognition of tumor cells was reduced after metallopeptidase inhibition or IDE silencing. Separate inhibition of the metallopeptidase and the proteasome impaired degradation of MAGE-A3 proteins, and simultaneous inhibition of both further stabilized MAGE-A3 proteins. These results suggest that MAGE-A3 proteins are degraded along two parallel pathways that involve either the proteasome or IDE and produce different sets of antigenic peptides presented by MHC class I molecules.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Parmentier N,Stroobant V,Colau D,de Diesbach P,Morel S,Chapiro J,van Endert P,Van den Eynde BJ

doi

10.1038/ni.1862

subject

Has Abstract

pub_date

2010-05-01 00:00:00

pages

449-54

issue

5

eissn

1529-2908

issn

1529-2916

pii

ni.1862

journal_volume

11

pub_type

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