Mice completely lacking immunoproteasomes show major changes in antigen presentation
Authors
Kincaid, Eleanor Z.Che, Jenny Wun-Yue
York, Ian
Escobar, Hernando
Reyes-Vargas, Eduardo
Delgado, Julio C.
Welsh, Raymond M.
Karow, Margaret L.
Murphy, Andrew J.
Valenzuela, David M.
Yancopoulos, George D.
Rock, Kenneth L.
Student Authors
Jenny Wun-Yue CheUMass Chan Affiliations
Department of PathologyDocument Type
Journal ArticlePublication Date
2011-12-25Keywords
Animals; Antigen Presentation; Dendritic Cells; Epitopes; Female; Graft Rejection; Histocompatibility Antigens Class I; Histocompatibility Antigens Class II; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Proteasome Endopeptidase ComplexImmunology and Infectious Disease
Immunopathology
Metadata
Show full item recordAbstract
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.Source
Kincaid EZ, Che JW, York I, Escobar H, Reyes-Vargas E, Delgado JC, Welsh RM, Karow ML, Murphy AJ, Valenzuela DM, Yancopoulos GD, Rock KL. Mice completely lacking immunoproteasomes show major changes in antigen presentation. Nat Immunol. 2011 Dec 25;13(2):129-35. doi: 10.1038/ni.2203. Link to article on publisher's websiteDOI
10.1038/ni.2203Permanent Link to this Item
http://hdl.handle.net/20.500.14038/33329PubMed ID
22197977Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1038/ni.2203