title: Mice completely lacking immunoproteasomes show major changes in antigen presentation.
abstract: The importance of immunoproteasomes to antigen presentation has been unclear because animals totally lacking immunoproteasomes had not been available. Having now developed mice lacking the three immunoproteasome catalytic subunits, we found that the dendritic cells of these mice had defects in presenting several major histocompatibility complex (MHC) class I epitopes. During viral infection in vivo, the presentation of a majority of MHC class I epitopes was markedly reduced in immunoproteasome-deficient animals compared with wild-type animals, whereas presentation of MHC class II peptides was unaffected. According to mass spectrometry, the repertoire of MHC class I-presented peptides was ∼50% different from that in wild-type mice, and these differences were sufficient to stimulate robust transplant rejection of wild-type cells in mutant mice. These results indicated that immunoproteasomes were more important in antigen presentation than previously thought.
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Eleanor Z
authors.initials: EZ
authors.lastname: Kincaid
authors.forename: Jenny W
authors.initials: JW
authors.lastname: Che
authors.forename: Ian
authors.initials: I
authors.lastname: York
authors.forename: Hernando
authors.initials: H
authors.lastname: Escobar
authors.forename: Eduardo
authors.initials: E
authors.lastname: Reyes-Vargas
authors.forename: Julio C
authors.initials: JC
authors.lastname: Delgado
authors.forename: Raymond M
authors.initials: RM
authors.lastname: Welsh
authors.forename: Margaret L
authors.initials: ML
authors.lastname: Karow
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Murphy
authors.forename: David M
authors.initials: DM
authors.lastname: Valenzuela
authors.forename: George D
authors.initials: GD
authors.lastname: Yancopoulos
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Rock
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000276:immunology*
chemical_list: D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D046988:Proteasome Endopeptidase Complex