Mice deficient in perforin, CD4+ T cells, or CD28-mediated signaling maintain the typical immunodominance hierarchies of CD8+ T-cell responses to influenza virus

CD8 T-cell (TCD8+) responses elicited by viral infection demonstrate the phenomenon of immunodominance: the numbers of TCD8+ responding to different viral peptides vary over a wide range in a reproducible manner for individuals with the same major histocompatibility complex class I alleles. To better understand immunodominance, we examined TCD8+ responses to multiple defined viral peptides following infection of mice with influenza virus. The immunodominance hierarchy of influenza virus-specific TCD8+ was not greatly perturbed by the absence of either perforin or T-helper cells or by interference with B7 (CD80)-mediated signaling. These findings indicate that costimulation by antigen-presenting cells (APCs) or killing of APCs by TCD8+ plays only a minor role in establishing the immunodominance hierarchy of antiviral TCD8+ in this system. This points to intrinsic features of the TCD8+ repertoire as major contributors to immunodominance.