Quantitation of CD8+ T-lymphocyte responses to multiple epitopes from simian virus 40 (SV40) large T antigen in C57BL/6 mice immunized with SV40, SV40 T-antigen-transformed cells, or vaccinia virus recombinants expressing full-length T antigen or epitope minigenes

Lawrence M. Mylin, Todd D. Schell, Debra Roberts, Melanie Epler, Alina Boesteanu, Edward J. Collins, Jeffrey A. Frelinger, Sebastian Joyce, Satvir S. Tevethia

Research output: Contribution to journalArticle

83 Scopus citations

Abstract

The cytotoxic T-lymphocyte response to wild-type simian virus 40 large tumor antigen (Tag) in C57BL/6 (H2b) mice is directed against three H2-Db- restricted epitopes, I, II/III, and V, and one H2-Kb-restricted epitope, IV. Epitopes I, II/III, and IV are immunodominant, while epitope V is immunorecessive. We investigated whether this hierarchical response was established in vivo or was due to differential expansion in vitro by using direct enumeration of CD8+ T lymphocytes with Tag epitope/major histocompatibility complex class I tetramers and intracellular gamma interferon staining. The results demonstrate that epitope IV-specific CD8+ cells dominated the Tag-specific response in vivo following immunization with full-length Tag while CD8+ T cells specific for epitopes I and II/III were detected at less than one-third of this level. The immunorecessive nature of epitope V was apparent in vivo, since epitope V-specific CD8+ T cells were undetectable following immunization with full-length Tag. In contrast, high levels of epitope V-specific CD8+ T lymphocytes were recruited in vivo following immunization and boosting with a Tag variant in which epitopes I, II/III, and IV had been inactivated. In addition, analysis of the T-cell receptor β (TCRβ) repertoire of Tag epitope-specific CD8+ cells revealed that multiple TCRβ variable regions were utilized for each epitope except Tag epitope II/III, which was limited to TCRβ10 usage. These results indicate that the hierarchy of Tag epitope-specific CD8+ T-cell responses is established in vivo.

Original languageEnglish (US)
Pages (from-to)6922-6934
Number of pages13
JournalJournal of virology
Volume74
Issue number15
DOIs
StatePublished - Aug 1 2000
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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