Nature Immunology
3, 1177 - 1184 (2002)
Published online: 18 November 2002; | doi:10.1038/ni860
The ER aminopeptidase ERAP1 enhances or limits antigen presentation by trimming epitopes to 8−9 residuesIan A. York1, Shih-Chung Chang2, Tomo Saric2, 3, Jennifer A. Keys1, Janice M. Favreau1, Alfred L. Goldberg2
& Kenneth L. Rock11
Department of Pathology, University of Massachusetts Medical Center, Worcester, MA 01655, USA. 2
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. 3
Present address: ATABIS GmbH, Cologne, Germany.
Correspondence should be addressed to Ian.York@umassmed.eduEndoplasmic 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- 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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