Mice completely lacking immunoproteasomes show major changes in antigen presentation
Immunology & Microbiology
Department of Pathology
Medical Subject Headings
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 Complex
Immunology and Infectious Disease | Immunopathology
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.
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Citation: 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 website
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.; and Rock, Kenneth L., "Mice completely lacking immunoproteasomes show major changes in antigen presentation" (2011). GSBS Student Publications. Paper 1856.