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The ER aminopeptidase ERAP1 enhances or limits antigen presentation by trimming epitopes to 8–9 residues

Nature Immunologyvolume 3pages11771184 (2002) | Download Citation



Endoplasmic reticulum (ER) aminopeptidase 1 (ERAP1) appears to be specialized to produce peptides presented on class I major histocompatibility complex molecules. We found that purified ERAP1 trimmed peptides that were ten residues or longer, but spared eight-residue peptides. In vivo, ERAP1 enhanced production of an eight-residue ovalbumin epitope from precursors extended on the NH2 terminus that were generated either in the ER or cytosol. Purified ERAP1 also trimmed nearly half the nine-residue peptides tested. By destroying such nine-residue peptides in normal human cells, ERAP1 reduced the overall supply of antigenic peptides. However, after interferon-γ treatment, which causes proteasomes to produce more NH2-extended antigenic precursors, ERAP1 increased the supply of peptides for MHC class I antigen presentation.

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We thank R. Welsh, M. Brehm, T. Vedvick and particularly L. Selin for the gifts of synthetic peptides; A. Hattori and M. Tsujimoto for recombinant ERAP1; L. Stern and B. Scearce for helpful discussions; and S. Trombley for assistance in preparing this manuscript. Supported by grants from the NIH (to K. L. R. and A. L. G.).

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Author notes

    • Tomo Saric

    Present address: ATABIS GmbH, Cologne, Germany


  1. Department of Pathology, University of Massachusetts Medical Center, Worcester, 01655, MA, USA

    • Ian A. York
    • , Jennifer A. Keys
    • , Janice M. Favreau
    •  & Kenneth L. Rock
  2. Department of Cell Biology, Harvard Medical School, Boston, 02115, MA, USA

    • Shih-Chung Chang
    • , Tomo Saric
    •  & Alfred L. Goldberg


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