Production of an antigenic peptide by insulin-degrading enzyme
(2010) Nature Immunology — Vol. 11, n° 5, p. 449-454 (2010)
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- 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.
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Parmentier, N., Stroobant, V., Colau, D., de Diesbach, P., Morel, S., Chapiro, J., van Endert, P., & Van den Eynde, B. (2010). Production of an antigenic peptide by insulin-degrading enzyme. Nature Immunology, 11(5), 449-454. https://doi.org/10.1038/ni.1862 (Original work published 2010)