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

Nature Immunology volume 3, pages 1177–1184 (2002)Cite this article

Abstract

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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Figure 1: Elimination of ERAP1 with siRNA reduces presentation of SIINFEKL.
Figure 2: Altering ERAP1 expression markedly affects human MHC class I surface expression.
Figure 3: Purified ERAP1 efficiently hydrolyzes peptides to eight or nine residues.
Figure 4: In IFN-γ–treated cells, eliminating ERAP1 reduces antigen presentation.

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Acknowledgements

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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  1. Tomo Saric

    Present address: ATABIS GmbH, Cologne, Germany

Authors and Affiliations

  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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York, I., Chang, SC., Saric, T. et al. The ER aminopeptidase ERAP1 enhances or limits antigen presentation by trimming epitopes to 8–9 residues. Nat Immunol 3, 1177–1184 (2002). https://doi.org/10.1038/ni860

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