Following influenza virus infection, the numbers of mouse T_CD8+ cells responding to five different determinants vary more than 50-fold in primary responses but less so in secondary responses. Surprisingly, each determinant elicits a highly diverse and highly sensitive T_CD8+ response. Inefficient antigen processing by virus-infected cells accounts for the poor immunogenicity of just one of the subdominant determinants. Overexpressing class I–peptide complexes using vaccinia virus revealed that the poor immunogenicity of two subdominant determinants reflects limitations in T cell responses unrelated to TCR diversity or sensitivity. Despite greatly enhanced expression, the immunodominant determinant is actually less immunogenic when overexpressed by vaccinia virus. Immunodominance is also modulated by determinant-specific variations in the capacity of T_CD8+ to suppress responses to other determinants.