Cutting edge: shift in antigen dependence by an antiviral MHC class Ib-restricted CD8 T cell response during persistent viral infection.

The requirement for Ag in maintaining memory CD8 T cells often differs between infections that are acutely resolved and those that persist. Using the mouse polyoma virus (PyV) persistent infection model, we recently described a novel CD8 T cell response directed to a PyV peptide presented by Q9, an MHC class Ib molecule. This antiviral Q9-restricted CD8 T cell response is characterized by a 3-mo expansion phase followed by a long-term plateau phase. In this study, we demonstrate that viral Ag is required for this protracted inflation phase but is dispensable for the maintenance of this Q9-restricted CD8 T cell response. Moreover, proliferation by memory T cells, not recruitment of naive PyV-specific T cells, is primarily responsible for Q9-restricted, anti-PyV CD8 T cell inflation. These data reveal a dynamic shift in Ag dependence by an MHC class Ib-restricted memory CD8 T cell response during a persistent viral infection.