T CELL IMMUNITY TO POLYOMA VIRUS-INDUCED TUMORS

  • Lukacher, Aron (PI)
  • LUKACHER, ARON (PI)
  • LUKACHER, ARON (PI)
  • LUKACHER, ARON (PI)
  • LUKACHER, ARON (PI)

Project: Research project

Project Details

Description

DESCRIPTION (Adapted from the Applicant's Abstract): Cytotoxic T lymphocytes
(CTL) play a role in host defense against neoplastic cells. Analysis of their
immunoregulation and effector mechanism is limited by (a) unknown tumor-
specific antigens, (b) experimental tumor models that do not reflect
"naturally-occurring" neoplastic disease and (c) polyclonal CTL responses.
Polyoma virus is a natural mouse pathogen capable of inducing a diverse
variety of epithelial and mesenchymal cell-derived tumors which are the same
cell types giving rise to the majority of human tumors. Inbred mouse strains
vary in their susceptibility to polyoma tumorigenesis. Resistance to polyoma
tumors is mediated by T-cells, with no apparent contribution from antiviral
antibody. A subset of H-2k mouse strains that carry an endogenous
superantigen encoded by the Mtv-7 provirus are susceptible to polyoma
tumorigenicity. Polyoma-specific CD8+ CTL in the resistant H-2k Mtv-7- mice
appear to express Vb6-T-cell receptor (TCR), which are deleted in H-2k Mtv-7+
mice. The principal investigator will test the hypothesis that immunity to
polyoma tumors is dominated by an oligoclonal CD8+Vb6+ CTL response directed
to a single viral epitope. Aim 1 is to determine whether polyoma-specific
CD8+Vb6+ CTL protect H-2k mice from polyoma tumors. The investigators have
isolated anti-polyoma CTL clones from resistant H-2k mice and found them to be
CD8+Vb6+. These CTL clones will enable the principal investigator to
determine the antigenic diversity of polyoma tumors. The final aim is to
compare TCR sequences of CD8+Vb6+ CTL lines which recognize the same viral
peptide-MHC complexes to determine the extent of conservation of the other TCR
domains, particularly the CDR3 regions. The availability of an oligoclonal,
monospecific anti-tumor CTL response in vivo will permit detailed
investigation of the induction, immunoregulation and tumoricidal mechanism(s)
of this T-cell subset, and thereby facilitate development of immunotherapeutic
strategies to neoplastic disease.
StatusFinished
Effective start/end date7/1/965/31/12

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