Prolonged antigen presentation following an acute virus infection requires direct and then cross-presentation

Antiviral CD8⁺ T cell recognition of MHC class I-peptide complexes on the surface of professional APCs is a requisite step in an effective immune response following many potentially lethal infections. Although MHC class I-peptide production is thought to be closely linked to the continued presence of virus, several studies have shown that the persistence of Ag presentation occurs for an extended period of time following the clearance of RNAviruses. However, the mechanism responsible for Ag presentation persistence following viral clearance was unknown until now. In this study, we used a recombinant DNA virus expressing different forms of a model Ag to study the mechanism of prolonged Ag presentation in mice. We determined that the persistence of Ag presentation consists of three distinct mechanistic phases, as follows: ongoing viral replication, persistence of virally infected cells, and crosspresentation of Ag. These data will allow manipulation of the form of Ag contained within viral vectors to produce the most effective and protective CD8⁺ T cell response to be generated following vaccination.