title: Late priming and variability of epitope-specific CD8+ T cell responses during a persistent virus infection.
abstract: 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.
authors.affiliation: Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Kemball
authors.forename: Eun D Han
authors.initials: ED
authors.lastname: Lee
authors.forename: Vaiva
authors.initials: V
authors.lastname: Vezys
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Pearson
authors.forename: Christian P
authors.initials: CP
authors.lastname: Larsen
authors.forename: Aron E
authors.initials: AE
authors.lastname: Lukacher
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000379:methods; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D002454:Cell Differentiation / Q000276:immunology; D045744:Cell Line, Tumor; D002678:Chimera / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D016056:Immunodominant Epitopes / Q000276:immunology*; D007156:Immunologic Memory / Q000235:genetics; D016130:Immunophenotyping; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011120:Polyomavirus / Q000276:immunology*; D027601:Polyomavirus Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology / Q000821:virology; D014412:Tumor Virus Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D017735:Virus Latency / Q000235:genetics / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes