Lytic cycle T cell epitopes are expressed in two distinct phases during MHV-68 infection

Murine herpesvirus-68 (MHV-68) is a type 2 gamma herpesvirus that productiv ely infects alveolar epithelial cells during the acute infection and establ ishes long-term latency in B cells and lung epithelial tells. In C57BL/6 mi ce, T cells specific for lytic cycle MHV-68 epitope p56/D-b dominate the ac ute phase of the infection, whereas T cells specific for another lytic cycl e epitope, p79/K-b, dominate later phases of infection. To further understa nd this response, we analyzed the kinetics of Ag presentation in vivo using a panel of lacZ-inducible T cell hybridomas specific for several lytic cyc le epitopes, including p56/D-b and D79/K-b. Two distinct peaks of Ag presen tation were observed. The first peak was at day 6 in the mediastinal lymph nodes and correlated with the initial pulmonary lytic infection. The second peak was at day 18 in both the mediastinal lymph nodes and spleen and corr elated with the peak of latent infection. Interestingly, the p56 epitope wa s detected only in the mediastinal lymph nodes at day 6 after infection whe reas the p79 epitope was predominantly presented in the spleen at day 18, s uggesting that differential epitope presentation drives the switch in T cel l responses to this virus. Phenotypic analysis of APCs at day 18 postinfect ion revealed that dendritic cells, macrophages, and B cells all presented l ytic cycle epitopes. Taken together, the data suggest that there is a resur gence of lytic cycle Ags in the spleen, which explains the kinetics and spe cificity of the T cell response to MHV-68.