title: The ER aminopeptidase ERAP1 enhances or limits antigen presentation by trimming epitopes to 8-9 residues.
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-gamma treatment, which causes proteasomes to produce more NH2-extended antigenic precursors, ERAP1 increased the supply of peptides for MHC class I antigen presentation.
authors.affiliation: Department of Pathology, University of Massachusetts Medical Center, Worcester, MA 01655, USA. Ian.York@umassmed.edu
authors.forename: Ian A
authors.initials: IA
authors.lastname: York
authors.forename: Shih-Chung
authors.initials: SC
authors.lastname: Chang
authors.forename: Tomo
authors.initials: T
authors.lastname: Saric
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Keys
authors.forename: Janice M
authors.initials: JM
authors.lastname: Favreau
authors.forename: Alfred L
authors.initials: AL
authors.lastname: Goldberg
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Rock
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D002460:Cell Line; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007931:Leucyl Aminopeptidase / Q000737:chemistry / Q000276:immunology*; D008024:Ligands; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology
chemical_list: D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D010047:Ovalbumin; D007931:Leucyl Aminopeptidase; C456799:puromycin-insensitive leucyl-specific aminopeptidase