To study the CD8+ T cell response against a mouse γ-herpes virus, we generated Kb-MHV-68-ORF8604–612RAG−/− CD8+ T cell receptor transnuclear (TN) mice as a source of virus-specific CD8+ T cells. Kb-ORF8-Tet+ CD8+ T cells, expanded in the course of a resolving MHV-68 infection, served as a source of nucleus donors. Various in vivo and ex vivo assay criteria demonstrated the fine specificity and functionality of TN cells. TN cells proliferated extensively in response to viral infection, helped control viral burden, and exhibited a phenotype similar to that of endogenous Kb-ORF8-Tet+ cells. When compared to OT-1 cells, TN cells displayed distinct properties in response to lymphopenia and cognate antigen stimulation, which may be attributable to the affinity of the TCR expressed by the TN cells. The availability of MHV-68-specific CD8+ TCR TN mice provides a new tool for investigating aspects of host-pathogen interactions unique to γ-herpes viruses.
