Resistance of polyoma virus-induced tumors correlates with CTL recognition of an immunodominant H-2D(k)-restricted epitope in the middle T protein

Aron E. Lukacher, Christopher S. Wilson

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

The natural mouse pathogen polyoma virus is highly oncogenic in H-2(k) mice carrying the endogenous superantigen encoded by the mouse mammary tumor provirus Mtv-7. This superantigen results in deletion of Vβ6 TCR-expressing polyoma-specific CD8+ CTL, which appear to be critical effectors against polyoma tumorigenesis. Here we have isolated cloned lines of CD8+ T cells from resistant (i.e., Mtv-7-) H-2(k) mice that specifically lyse syngeneic polyoma virus-infected cells and polyoma tumor cells. Nearly all these CTL clones express Vβ6 and are restricted in their recognition of virus-infected cells by H-2D(k). Screening a panel of synthetic peptides predicted to bind to D(k) for which no consensus peptide binding motif is known, we identified a peptide corresponding to a nine-amino acid sequence in the carboxyl- terminus of the middle T (MT) protein (amino acid 389-397) that was recognized by all the Vβ6+CD8+ CTL clones. The inability of MT389- 397-reactive CTL to recognize cells infected with a mutant polyoma virus encoding a MT truncated just proximal to this sequence indicates that MT389-397 is a naturally processed peptide. The frequencies of precursor CTL specific for polyoma virus and MT389-397 peptide were similar, indicating that MT389-397 is the immunodominant epitope in H- 2(k) mice. In addition, polyoma-infected resistant mice posses a 10- to 20- fold higher MT389-397-specific precursor CTL frequency than susceptible mice. This highly focused CTL response to polyoma virus provides a valuable animal model to investigate the in vivo activity of CTL against virus-induced neoplasia.

Original languageEnglish (US)
Pages (from-to)1724-1734
Number of pages11
JournalJournal of Immunology
Volume160
Issue number4
StatePublished - Feb 15 1998

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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