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Publication : Mixed proteasomes function to increase viral peptide diversity and broaden antiviral CD8+ T cell responses.

First Author  Zanker D Year  2013
Journal  J Immunol Volume  191
Issue  1 Pages  52-9
PubMed ID  23709680 Mgi Jnum  J:205374
Mgi Id  MGI:5544693 Doi  10.4049/jimmunol.1300802
Citation  Zanker D, et al. (2013) Mixed proteasomes function to increase viral peptide diversity and broaden antiviral CD8+ T cell responses. J Immunol 191(1):52-9
abstractText  The three proteasome subunits with proteolytic activity are encoded by standard or immunoproteasome genes. Many proteasomes expressed by normal cells and cells exposed to cytokines are "mixed", that is, contain both standard and immunoproteasome subunits. Using a panel of 38 defined influenza A virus-derived epitopes recognized by C57BL/6 mouse CD8(+) T cells, we used mice with targeted disruption of beta1i, beta2i, or beta5i/beta2i genes to examine the contribution of mixed proteasomes to the immunodominance hierarchy of antiviral CD8(+) T cells. We show that each immunoproteasome subunit has large effects on the primary and recall immunodominance hierarchies due to modulating both the available T cell repertoire and generation of individual epitopes as determined both biochemically and kinetically in Ag presentation assays. These findings indicate that mixed proteasomes function to enhance the diversity of peptides and support a broad CD8(+) T cell response.
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