1 The CD8 T cell response against Murine gamma herpes virus (MHV-68) is directed towards a broad repertoire of epitopes from both early and late antigens

2 Infection of mice with murine gamma herpes virus (MHV-68) robustly activates CD8 T cells, but only six Class I MHC restricted epitopes have been described to date for the widely used H-2b haplotype mice. To explore the specificity and kinetics of the CTL response in MHV-68 infected C57BL/6 mice, we screened for H-2Kb and H-2Db restricted epitopes using a set of 384 candidate epitopes in a MHC tetramer based approach, and identified 19 new epitopes in 16 different ORFs. Of the six known H-2Kb-and H-2Db-restricted epitopes, we confirmed a response against three and did not detect CD8 T cell specific responses for the remaining three. The peak of the CD8 T cell response to most peptides occurs between 6 and 10 days post infection (dpi). The respective MHC tetramer-positive CD8 T cells display an activated/effector phenotype (CD62lo and CD44hi) and produce IFN-γ upon peptide stimulation ex vivo. MHV-68 infection in vivo elicits a response to multiple viral epitopes, derived from both early and late viral antigens, illustrating a far broader T cell repertoire and more rapid activation than previously recorded. ACC EP