Late priming and variability of epitope-specific CD8+ T cell responses during a persistent virus infection

Christopher C. Kemball, Eun D.Han Lee, Vaiva Vezys, Thomas C. Pearson, Christian P. Larsen, Aron E. Lukacher

Research output: Contribution to journalArticlepeer-review

69 Scopus citations


Control of persistently infecting viruses requires that antiviral CD8 + T cells sustain their numbers and effector function. In this study, we monitored epitope-specific CD8+ T cells during acute and persistent phases of infection by polyoma virus, a mouse pathogen that is capable of potent oncogenicity. We identified several novel polyoma-specific CD8+ T cell epitopes in C57BL/6 mice, a mouse strain highly resistant to polyoma virus-induced tumors. Each of these epitopes is derived from the viral T proteins, nonstructural proteins produced by both productively and nonproductively (and potentially transformed) infected cells. In contrast to CD8+ T cell responses described in other microbial infection mouse models, we found substantial variability between epitope-specific CD8 + T cell responses in their kinetics of expansion and contraction during acute infection, maintenance during persistent infection, as well as their expression of cytokine receptors and cytokine profiles. This epitope-dependent variability also extended to differences in maturation of functional avidity from acute to persistent infection, despite a narrowing in TCR repertoire across all three specificities. Using a novel minimal myeloablation-bone marrow chimera approach, we visualized priming of epitope-specific CD8+ T cells during persistent virus infection. Interestingly, epitope-specific CD8+ T cells differed in CD62L-selectin expression profiles when primed in acute or persistent phases of infection, indicating that the context of priming affects CD8+ T cell heterogeneity. In summary, persistent polyoma virus infection both quantitatively and qualitatively shapes the antiviral CD8+ T cell response.

Original languageEnglish (US)
Pages (from-to)7950-7960
Number of pages11
JournalJournal of Immunology
Issue number12
StatePublished - Jun 15 2005


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