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* Clinic for Radiotherapy, University Hospital of Freiburg, Freiburg, Germany;
Institut National de la Santé et de la Recherche Médicale Unité 580, Paris, France and Université Paris Descartes, Paris, France;
Institute for Medical Microbiology and Hygiene, Department of Immunology, University of Freiburg, Freiburg, Germany;
Institute for Medical Microbiology and Hygiene, Department of Virology, University of Freiburg, Freiburg, Germany; and
¶ Max-Planck Institute of Immunobiology, Freiburg, Germany
Endoplasmic reticulum-associated aminopeptidase 1 (ERAP1) is involved in the final processing of endogenous peptides presented by MHC class I molecules to CTLs. We generated ERAP1-deficient mice and analyzed cytotoxic responses upon infection with three viruses, including lymphocytic choriomeningitis virus, which causes vigorous T cell activation and is controlled by CTLs. Despite pronounced effects on the presentation of selected epitopes, the in vivo cytotoxic response was altered for only one of several epitopes tested. Moreover, control of lymphocytic choriomeningitis virus was not impaired in the knockout mice. Thus, we conclude that lack of ERAP1 has little influence on antiviral immunohierarchies and antiviral immunity in the infections studied. We also focused on the role of ERAP1 in cross-presentation. We demonstrate that ERAP1 is required for efficient cross-presentation of cell-associated Ag and of OVA/anti-OVA immunocomplexes. Surprisingly, however, ERAP1 deficiency has no effect on cross-presentation of soluble OVA, suggesting that for soluble exogenous proteins, final processing may not take place in an environment containing active ERAP1.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by a grant from the Forschungskommission of the Medical Faculty of the University of Freiburg (NIE346/04; to G.N.).
2 Address correspondence and reprint requests to Dr. Gabriele Niedermann, Clinic for Radiotherapy, University Hospital of Freiburg, D-79106 Freiburg, Germany. E-mail address: gabriele.niedermann{at}uniklinik-freiburg.de
3 Abbreviations used in this paper: ER, endoplasmic reticulum; BM, bone marrow; DC, dendritic cell; ERAP, ER-associated aminopeptidase; ID, immunodominant; KO, knockout; LCMV, lymphocytic choriomeningitis virus; NP, nuclear protein; SD, subdominant; VV, vaccinia virus; wt, wild type.
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