title: The role of endoplasmic reticulum-associated aminopeptidase 1 in immunity to infection and in cross-presentation.
abstract: 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.
authors.affiliation: Clinic for Radiotherapy, University Hospital of Freiburg, Freiburg, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Firat
authors.forename: Loredana
authors.initials: L
authors.lastname: Saveanu
authors.forename: Peter
authors.initials: P
authors.lastname: Aichele
authors.forename: Peter
authors.initials: P
authors.lastname: Staeheli
authors.forename: Jisen
authors.initials: J
authors.lastname: Huai
authors.forename: Simone
authors.initials: S
authors.lastname: Gaedicke
authors.forename: Ahmed
authors.initials: A
authors.lastname: Nil
authors.forename: Gilles
authors.initials: G
authors.lastname: Besin
authors.forename: Benoît
authors.initials: B
authors.lastname: Kanzler
authors.forename: Peter
authors.initials: P
authors.lastname: van Endert
authors.forename: Gabriele
authors.initials: G
authors.lastname: Niedermann
mesh_terms: D000626:Aminopeptidases / Q000172:deficiency / Q000276:immunology*; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D000936:Antigen-Antibody Complex / Q000235:genetics / Q000276:immunology; D001117:Arenaviridae Infections / Q000235:genetics / Q000276:immunology*; D003429:Cross Reactions / Q000235:genetics / Q000276:immunology; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000936:Antigen-Antibody Complex; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D015778:Minor Histocompatibility Antigens; D000626:Aminopeptidases; C509944:ERAP1 protein, mouse