Nature Immunology
6, 689 - 697 (2005)
Published online: 22 May 2005; | doi:10.1038/ni1208
Concerted peptide trimming by human ERAP1 and ERAP2 aminopeptidase complexes in the endoplasmic reticulumLoredana Saveanu1, Oliver Carroll1, Vivian Lindo2, Margarita Del Val3, Daniel Lopez3, Yves Lepelletier4, Fiona Greer2, Lutz Schomburg5, Doriana Fruci1, 7, Gabriele Niedermann6, 7
& Peter M van Endert11
Institut National de la Sante et Recherche Médicale Unité 580; Université René Descartes Paris 5, 75015
Paris, France. 2
M-SCAN, Fishponds Close, Wokingham, Berkshire
RG41 2TZ, UK. 3
Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28220
Majadahonda, Spain. 4
Centre National de la Recherche Scientifique UMR 8147, Necker Institute, 75015
Paris, France. 5
Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin, 10117
Berlin, Germany. 6
Max-Planck Institut für Immunbiologie, 79108
Freiburg, Germany. 7
Present addresses: Research Center Ospedale Bambino Gesù, 00165
Rome, Italy (D.F.) and Clinic of Radiation Oncology, Experimental Division, University Clinic, Freiburg, Germany (G.N.).
Correspondence should be addressed to Peter M van Endert vanender@necker.frThe generation of many HLA class I peptides entails a final trimming step in the endoplasmic reticulum that, in humans, is accomplished by two 'candidate' aminopeptidases. We show here that one of these, ERAP1, was unable to remove several N-terminal amino acids that were trimmed efficiently by the second enzyme, ERAP2. This trimming of a longer peptide required the concerted action of both ERAP1 and ERAP2, both for in vitro digestion and in vivo for cellular antigen presentation. ERAP1 and ERAP2 localized together in vivo and associated physically in complexes that were most likely heterodimeric. Thus, the human endoplasmic reticulum is equipped with a pair of trimming aminopeptidases that have complementary functions in HLA class I peptide presentation.
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