Nature Immunology
3, 1169 - 1176 (2002)
Published online: 18 November 2002; | doi:10.1038/ni859
An IFN- −induced aminopeptidase in the ER, ERAP1, trims precursors to MHC class I−presented peptidesTomo Saric1, 4, Shih-Chung Chang1, Akira Hattori2, Ian A. York3, Shirley Markant1, Kenneth L. Rock3, Masafumi Tsujimoto2
& Alfred L. Goldberg11
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. 2
Laboratory of Cellular Biochemistry, RIKEN, 2-1 Hirosawa, Wako, Saitama, 351-0198 Japan. 3
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 06155, USA. 4
Present address: ATABIS GmbH, Joseph-Stelzmann Str. 50, 50931 Cologne, Germany.
Correspondence should be addressed to Alfred L. Goldberg alfred_goldberg@hms.harvard.eduPrecursors to major histocompatibility complex (MHC) class I−presented peptides with extra NH2-terminal residues can be efficiently trimmed to mature epitopes in the endoplasmic reticulum (ER). Here, we purified from liver microsomes a lumenal, soluble aminopeptidase that removes NH2-terminal residues from many antigenic precursors. It was identified as a metallopeptidase named "adipocyte-derived leucine" or "puromycin-insensitive leucine-specific" aminopeptidase. However, because we localized it to the ER, we propose it be renamed ER−aminopeptidase 1 (ERAP1). ERAP1 is inhibited by agents that block precursor trimming in ER vesicles and although it trimmed NH2-extended precursors, it spared presented peptides of 8 amino acid and less. Like other proteins involved in antigen presentation, ERAP1 is induced by interferon- . When overexpressed in vivo, we found that ERAP1 stimulates the processing and presentation of an antigenic precursor in the ER.
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