Selection and behavior of inflationary CD8 T-cell populations during mirine cytomegalovirus infection

Cytomegalovirus (CMV) establishes lifelong infection and drives “memory inflation,” a persistent CD8 T-cell response with effector characteristics. This property makes CMV an attractive vaccine vector, yet the mechanisms determining which viral epitopes inflate remain unclear. Using murine CMV encoding the SIINFEKL epitope, we show that epitope placement within the viral genome influences immunodominance, with SIINFEKL at the IE2 locus driving strong inflation. Coinfection experiments reveal that antigen availability at the level of antigen-presenting cells shapes inflationary selection. Additionally, intravenous peptide administration boosted both inflationary and central memory responses, suggesting a strategy for enhancing CMV-based vaccines and challenging assumptions about peptide-induced tolerance.