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Activation of low avidity CTL specific for a self epitope results in tumor rejection but not autoimmunity

Academic Article
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Overview

authors

  • Morgan, D. J.
  • Kreuwel, H. T. C.
  • Fleck, S.
  • Levitsky, H. I.
  • Pardoll, D. M.
  • Sherman, Linda

publication date

  • January 1998

journal

  • Journal of Immunology  Journal

abstract

  • To determine how self-tolerance can alter the ability of the immune system to respond against tumor-associated Ags that are also expressed by normal tissue, we designed experiments in which the same protein was expressed both as a tumor Ag and as a transgene product. Unlike conventional BALB/c mice that rejected renal carcinoma cells transfected with the influenza virus hemagglutinin (Renca-HA), transgenic mice that are tolerant of HA due to its expression as a self-Ag on pancreatic islet beta cells, (Ins-HA mice) supported progressive growth of these tumor cells. However, when Ins-HA mice were immunized with a recombinant strain of vaccinia virus expressing the dominant H-2Kd peptide epitope of HA before receiving Renca-HA cells, they too were able to reject the tumor cells. Rejection of Renca-HA cells by immunized Ins-HA mice was found to be associated with the generation of CTL having much lower avidity for target cells presenting the KdHA epitope than CTL from immunized conventional BALB/c mice. Significantly, we show that self-tolerance to the HA Ag is quantitative rather then absolute, and that vaccination of Ins-HA mice can activate low avidity KdHA-specific CD8+ T cells that are able to reject tumor cells expressing high levels of HA, yet these mice remain tolerant of pancreatic islet beta cells expressing HA.

subject areas

  • Animals
  • Autoimmunity
  • Cell Division
  • Epitopes, T-Lymphocyte
  • Graft Rejection
  • H-2 Antigens
  • Hemagglutinins
  • Influenza A virus
  • Kidney Neoplasms
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Neoplasm Transplantation
  • Peptide Fragments
  • T-Lymphocytes, Cytotoxic
  • Tumor Cells, Cultured
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Identity

International Standard Serial Number (ISSN)

  • 0022-1767

PubMed ID

  • 9551898
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Additional Document Info

start page

  • 643

end page

  • 651

volume

  • 160

issue

  • 2

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