Current knowledge about the dynamics of antigen presentation to T cells during viral infection is very poor despite being of fundamental importance to our understanding of anti-viral immunity. We have used advanced mass spectrometry to simultaneously quantify the presentation of vaccinia virus peptide-MHC complexes (epitopes) on infected cells and the amounts of their source antigens at multiple times after infection. The results show a startling 10,000-fold range in abundance as well as strikingly different kinetics across the epitopes monitored. The tight correlation between onset of protein expression and epitope display for most antigens provides the strongest support to date that antigen presentation is largely linked to translation and not later degradation of antigens. Finally, using data independent acquisition approaches (SWATH-MS) we have monitored all viral and host cell proteins providing a global view of viral antigen expression and host cell responses. This study highlights the complexity of viral antigen presentation and demonstrates the weakness of simple models that assume total protein levels are directly linked to epitope presentation and immunogenicity.