Dissecting the Multifactorial Causes of Immunodominance in Class I–Restricted T Cell Responses to Viruses Academic Article uri icon

abstract

  • Following influenza virus infection, the numbers of mouse TCD8+ 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 TCD8+ 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 TCD8+ to suppress responses to other determinants.

authors

  • Chen, Weisan
  • Antón, Luis C
  • Bennink, Jack R
  • Yewdell, Jonathan W

publication date

  • January 2000