Dissecting the multifactorial causes of immunodominance in class I-restricted T cell responses to viruses

Following influenza virus infection, the numbers of mouse T-CD8+ cells resp onding to five different determinants vary more than 50-fold in primary res ponses but less so in secondary responses. Surprisingly, each determinant e licits a highly diverse and highly sensitive T-CD8+ response. Inefficient a ntigen processing by virus-infected cells accounts for the poor immunogenic ity of just one of the subdominant determinants. Over-expressing class I-pe ptide complexes using vaccinia virus revealed that the poor immunogenicity of two subdominant determinants reflects limitations in T cell responses un related to TCR diversity or sensitivity. Despite greatly enhanced expressio n, the immunodominant determinant is actually less immunogenic when overexp ressed by vaccinia virus. Immunodominance is also modulated by determinant- specific variations in the capacity of T-CD8+ to suppress responses to othe r determinants.