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*
Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105; and
Department of Pathology, University of Tennessee, Memphis, TN 38111
Murine herpesvirus-68 (MHV-68) is a type 2 
herpesvirus that
productively infects alveolar epithelial cells during the acute
infection and establishes long-term latency in B cells and lung
epithelial cells. In C57BL/6 mice, T cells specific for lytic cycle
MHV-68 epitope p56/Db dominate the acute phase of the
infection, whereas T cells specific for another lytic cycle epitope,
p79/Kb, dominate later phases of infection. To further
understand this response, we analyzed the kinetics of Ag presentation
in vivo using a panel of lacZ-inducible T cell
hybridomas specific for several lytic cycle epitopes, including
p56/Db and p79/Kb. Two distinct peaks of Ag
presentation 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 correlated with the peak of latent infection.
Interestingly, the p56 epitope was detected only in the mediastinal
lymph nodes at day 6 after infection whereas the p79 epitope was
predominantly presented in the spleen at day 18, suggesting that
differential epitope presentation drives the switch in T cell responses
to this virus. Phenotypic analysis of APCs at day 18 postinfection
revealed that dendritic cells, macrophages, and B cells all presented
lytic cycle epitopes. Taken together, the data suggest that there is a
resurgence of lytic cycle Ags in the spleen, which explains the
kinetics and specificity of the T cell response to
MHV-68.
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