Altered immunodominance hierarchies of influenza A virus-specific H-2b-restricted CD8+ T cells in the absence of terminal deoxynucleotidyl transferase

Immunodominance is considered an obstacle to successful T cell-based vaccination, and constant efforts are made to uncover the underlying mechanisms for this phenomenon. We have examined the contribution of terminal deoxynucleotidyl transferase (TdT), whose function accounts for approximately 90% of T cell receptor diversity, to dominance hierarchies of H-2(b)-restricted flu-specific TCD8(+). Using intracellular cytokine staining to quantitatively detect epitope-specific TCD8(+), we demonstrate that TdT-deficient mice exhibit a distinct hierarchical pattern in their primary and recall TCD8(+) responses to influenza A viruses, which results from skewed responsiveness towards select influenza epitopes. Our data establish a link between TdT and immunodominance in H-2(b)-restricted antiviral TCD8(+) responses.