Journal
NATURE IMMUNOLOGY
Volume 13, Issue 2, Pages 129-135Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.2203
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Funding
- University of Massachusetts Diabetes and Endocrinology Research Center core resources [DK32520]
- US National Institutes of Health [5R01A1020248-29, 5T32A107349-19, T32CA130807-02, R37AI017672, R01AI081675, U01-AI073871]
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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 similar to 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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