A virus-specific CD8 T cell immunodominance hierarchy determined by antigen dose and precursor frequencies

Abstract

Immunodominance hierarchies are a substantial, but poorly understood, characteristic of CD8+ T cell-mediated immunity. Factors influencing the differential responses to the influenza A virus nucleoprotein (NP 366-374) and acid polymerase (PA224-233) peptides presented by H2Db have been analyzed by disabling (N5→Q substitution) these peptides in their native configuration, then expressing them in the viral neuraminidase protein. This strategy of shifting epitopes within the same viral context resulted in an apparent equalization of D bNP366 [epitope consisting of viral nucleoprotein (NP) amino acid residues 366-374 complexed with the H2Db MHC class I glycoprotein] and DbPA224 (H2Db+PA 224-233..