CD8 T-cell (T_CD8+) responses elicited by viral infection demonstrate the phenomenon of immunodominance: the numbers of T_CD8+ 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 T_CD8+ responses to multiple defined viral peptides following infection of mice with influenza virus. The immunodominance hierarchy of influenza virus-specific T_CD8+ 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 T_CD8+ plays only a minor role in establishing the immunodominance hierarchy of antiviral T_CD8+ in this system. This points to intrinsic features of the T_CD8+ repertoire as major contributors to immunodominance.