The role of endoplasmic reticulum-associated aminopeptidase 1 in immunity to infection and in cross-presentation.
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.
Firat
Elke
E
Clinic for Radiotherapy, University Hospital of Freiburg, Freiburg, Germany.
Saveanu
Loredana
L
Aichele
Peter
P
Staeheli
Peter
P
Huai
Jisen
J
Gaedicke
Simone
S
Nil
Ahmed
A
Besin
Gilles
G
Kanzler
Benoît
B
van Endert
Peter
P
Niedermann
Gabriele
G
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*
D000936:Antigen-Antibody Complex; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D015778:Minor Histocompatibility Antigens; D000626:Aminopeptidases; C509944:ERAP1 protein, mouse