Immunoproteasome Subunit Deficiencies Impact Differentially on Two Immunodominant Influenza Virus-Specific CD8+ T Cell Responses

Abstract

Primary CD8+ T cell (TCD8+) responses to viruses are directed toward multiple Ags and shaped by both the level of Ag presentation and the underlying Ag-specific TCD8+ repertoire. The relative importance of these factors in deciding the hierarchy of TCD8+ responses and how they are influenced by the immunoproteasome are not well understood. Using an influenza infection model in mice deficient in various immunoproteasome subunits, we observe that Ag presentation and TCD8+ repertoire are altered in an epitope-specific and immunoproteasome subunit-dependent manner. More importantly, we find that the level of Ag presentation and the extent of the underlying repertoire can work either alone or in concert to determine definitively the magnitude of the individual TCD8+ responses and hence the overall TCD8+ hierarchy. Together, these results provide a clearer understanding of how immunodominance hierarchies are established.