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Mixed Proteasomes Function To Increase Viral Peptide Diversity and Broaden Antiviral CD8+ T Cell Responses

Many proteasomes expressed by normal cells and cells exposed to cytokines are "mixed", that is, contain both standard and immunoproteasome subunits.

Authors:
Zanker D, Waithman J, Yewdell JW, Chen W

Authors notes:
Journal of immunology. 2013 2013-Jul-1;191(1):52-59

Keywords:
Proteasome, cytokines, T cell response, antigen presentation, peptides

Abstract:
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.

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.