Efficient induction of cytotoxic CD8+ T cells against exogenous proteins: establishment and characterization of a T cell line specific for the membrane protein ActA of Listeria monocytogenes

Eur J Immunol. 1998 Sep;28(9):2630-9. doi: 10.1002/(SICI)1521-4141(199809)28:09<2630::AID-IMMU2630>3.0.CO;2-Z.

Abstract

The property of listeriolysin (LLO) to introduce soluble passenger proteins into the cytosol of antigen-presenting cells allows the induction of CD8+ cytotoxic T cells against such antigens. To overcome the potential problem of presentation of the immunodominant epitope LL091-99 by H-2Kd, a variant LLO92A was established in which Tyr 92 was replaced by Ala. Immunization of BALB/c mice with purified LLO92A failed to stimulate cytotoxic T cells specific for either the epitope LLO91-99 or for any other LLO-derived peptide. Injection of mixtures of purified LLO92A and soluble nucleoprotein (NP) of influenza virus into mice resulted in a strong cytotoxic T cell response exclusively directed against NP. The LLO92A variant was successfully used to generate, propagate and characterize a CD8 T cell line specific for the membrane-bound virulence factor ActA of Listeria monocytogenes. Interestingly, wildtype ActA bound to the surface of live L. monocytogenes was not presented by MHC class I molecules to the CD8+ T cell line.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation
  • Antigens, Bacterial / immunology
  • Bacterial Proteins / immunology*
  • Bacterial Toxins*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Line*
  • Cytotoxicity, Immunologic*
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / immunology
  • Hemolysin Proteins
  • Listeria monocytogenes / immunology*
  • Membrane Proteins / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mutation

Substances

  • Antigens, Bacterial
  • Bacterial Proteins
  • Bacterial Toxins
  • Heat-Shock Proteins
  • Hemolysin Proteins
  • Membrane Proteins
  • actA protein, Listeria monocytogenes
  • hlyA protein, Listeria monocytogenes