Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1992 Jun 1;175(6):1531–1538. doi: 10.1084/jem.175.6.1531

CD8+ T cells specific for a single nonamer epitope of Listeria monocytogenes are protective in vivo

PMCID: PMC2119257  PMID: 1375265

Abstract

Class I major histocompatibility complex (MHC)-restricted CD8+ T cells have been demonstrated to be effective mediators of both acquired and adoptive immunity to the intracellular bacterium Listeria monocytogenes. We have recently determined that L. monocytogenes- infected H-2d mice recognize a nonamer peptide, residues 91-99, of the secreted protein listeriolysin O (LLO), in a H-2Kd-restricted fashion. In this report we have generated CD8+ T cell lines with specificity for LLO 91-99 in the context of H-2Kd by in vitro stimulation with P815 (H- 2d) cells transfected with LLO. These CD8+ lines have been generated from immune donors after sublethal infection with L. monocytogenes, or after in vivo immunization with syngeneic spleen cells coated with synthetic LLO 91-99 peptide. LLO-specific CD8+ T cells derived from either protocol were capable of significant protection against L. monocytogenes infection. The in vivo protection by these CD8+ T cell lines has been shown to be solely due to recognition of LLO 91-99 in the context of H-2Kd. These studies demonstrate that CD8+ T cell immunity to a single, naturally produced peptide epitope has the potential for significant protection in a bacterial infection. Thus, the allele-specific motif approach to epitope prediction has identified a naturally produced bacterial epitope with biological relevance.

Full Text

The Full Text of this article is available as a PDF (834.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alexander M. A., Damico C. A., Wieties K. M., Hansen T. H., Connolly J. M. Correlation between CD8 dependency and determinant density using peptide-induced, Ld-restricted cytotoxic T lymphocytes. J Exp Med. 1991 Apr 1;173(4):849–858. doi: 10.1084/jem.173.4.849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berche P., Gaillard J. L., Sansonetti P. J. Intracellular growth of Listeria monocytogenes as a prerequisite for in vivo induction of T cell-mediated immunity. J Immunol. 1987 Apr 1;138(7):2266–2271. [PubMed] [Google Scholar]
  3. Bishop D. K., Hinrichs D. J. Adoptive transfer of immunity to Listeria monocytogenes. The influence of in vitro stimulation on lymphocyte subset requirements. J Immunol. 1987 Sep 15;139(6):2005–2009. [PubMed] [Google Scholar]
  4. Brunt L. M., Portnoy D. A., Unanue E. R. Presentation of Listeria monocytogenes to CD8+ T cells requires secretion of hemolysin and intracellular bacterial growth. J Immunol. 1990 Dec 1;145(11):3540–3546. [PubMed] [Google Scholar]
  5. Buchmeier N. A., Schreiber R. D. Requirement of endogenous interferon-gamma production for resolution of Listeria monocytogenes infection. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7404–7408. doi: 10.1073/pnas.82.21.7404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Carbone F. R., Bevan M. J. Class I-restricted processing and presentation of exogenous cell-associated antigen in vivo. J Exp Med. 1990 Feb 1;171(2):377–387. doi: 10.1084/jem.171.2.377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Carbone F. R., Moore M. W., Sheil J. M., Bevan M. J. Induction of cytotoxic T lymphocytes by primary in vitro stimulation with peptides. J Exp Med. 1988 Jun 1;167(6):1767–1779. doi: 10.1084/jem.167.6.1767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cossart P., Mengaud J. Listeria monocytogenes. A model system for the molecular study of intracellular parasitism. Mol Biol Med. 1989 Oct;6(5):463–474. [PubMed] [Google Scholar]
  9. Czuprynski C. J., Brown J. F. Effects of purified anti-Lyt-2 mAb treatment on murine listeriosis: comparative roles of Lyt-2+ and L3T4+ cells in resistance to primary and secondary infection, delayed-type hypersensitivity and adoptive transfer of resistance. Immunology. 1990 Sep;71(1):107–112. [PMC free article] [PubMed] [Google Scholar]
  10. Dailey M. O., Gallatin W. M., Weissman I. L. The in vivo behavior of T cell clones: altered migration due to loss of the lymphocyte surface homing receptor. J Mol Cell Immunol. 1985;2(1):27–36. [PubMed] [Google Scholar]
  11. Dunn P. L., North R. J. Early gamma interferon production by natural killer cells is important in defense against murine listeriosis. Infect Immun. 1991 Sep;59(9):2892–2900. doi: 10.1128/iai.59.9.2892-2900.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dunn P. L., North R. J. Limitations of the adoptive immunity assay for analyzing anti-Listeria immunity. J Infect Dis. 1991 Nov;164(5):878–882. doi: 10.1093/infdis/164.5.878. [DOI] [PubMed] [Google Scholar]
  13. Dunn P. L., North R. J. Resolution of primary murine listeriosis and acquired resistance to lethal secondary infection can be mediated predominantly by Thy-1+ CD4- CD8- cells. J Infect Dis. 1991 Nov;164(5):869–877. doi: 10.1093/infdis/164.5.869. [DOI] [PubMed] [Google Scholar]
  14. Falk K., Rötzschke O., Deres K., Metzger J., Jung G., Rammensee H. G. Identification of naturally processed viral nonapeptides allows their quantification in infected cells and suggests an allele-specific T cell epitope forecast. J Exp Med. 1991 Aug 1;174(2):425–434. doi: 10.1084/jem.174.2.425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Falk K., Rötzschke O., Stevanović S., Jung G., Rammensee H. G. Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature. 1991 May 23;351(6324):290–296. doi: 10.1038/351290a0. [DOI] [PubMed] [Google Scholar]
  16. Gunning P., Leavitt J., Muscat G., Ng S. Y., Kedes L. A human beta-actin expression vector system directs high-level accumulation of antisense transcripts. Proc Natl Acad Sci U S A. 1987 Jul;84(14):4831–4835. doi: 10.1073/pnas.84.14.4831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Jardetzky T. S., Lane W. S., Robinson R. A., Madden D. R., Wiley D. C. Identification of self peptides bound to purified HLA-B27. Nature. 1991 Sep 26;353(6342):326–329. doi: 10.1038/353326a0. [DOI] [PubMed] [Google Scholar]
  18. Kaufmann S. H., Rodewald H. R., Hug E., De Libero G. Cloned Listeria monocytogenes specific non-MHC-restricted Lyt-2+ T cells with cytolytic and protective activity. J Immunol. 1988 May 1;140(9):3173–3179. [PubMed] [Google Scholar]
  19. Kaufmann S. H., Simon M. M., Hahn H. Specific Lyt 123 cells are involved in protection against Listeria monocytogenes and in delayed-type hypersensitivity to listerial antigens. J Exp Med. 1979 Oct 1;150(4):1033–1038. doi: 10.1084/jem.150.4.1033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Khusmith S., Charoenvit Y., Kumar S., Sedegah M., Beaudoin R. L., Hoffman S. L. Protection against malaria by vaccination with sporozoite surface protein 2 plus CS protein. Science. 1991 May 3;252(5006):715–718. doi: 10.1126/science.1827210. [DOI] [PubMed] [Google Scholar]
  21. Kiderlen A. F., Kaufmann S. H., Lohmann-Matthes M. L. Protection of mice against the intracellular bacterium Listeria monocytogenes by recombinant immune interferon. Eur J Immunol. 1984 Oct;14(10):964–967. doi: 10.1002/eji.1830141019. [DOI] [PubMed] [Google Scholar]
  22. Lane F. C., Unanue E. R. Requirement of thymus (T) lymphocytes for resistance to listeriosis. J Exp Med. 1972 May 1;135(5):1104–1112. doi: 10.1084/jem.135.5.1104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lukacs K., Kurlander R. Lyt-2+ T cell-mediated protection against listeriosis. Protection correlates with phagocyte depletion but not with IFN-gamma production. J Immunol. 1989 Apr 15;142(8):2879–2886. [PubMed] [Google Scholar]
  24. MACKANESS G. B. Cellular resistance to infection. J Exp Med. 1962 Sep 1;116:381–406. doi: 10.1084/jem.116.3.381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Mackaness G. B. The influence of immunologically committed lymphoid cells on macrophage activity in vivo. J Exp Med. 1969 May 1;129(5):973–992. doi: 10.1084/jem.129.5.973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Mielke M. E., Ehlers S., Hahn H. T-cell subsets in delayed-type hypersensitivity, protection, and granuloma formation in primary and secondary Listeria infection in mice: superior role of Lyt-2+ cells in acquired immunity. Infect Immun. 1988 Aug;56(8):1920–1925. doi: 10.1128/iai.56.8.1920-1925.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Mielke M. E., Niedobitek G., Stein H., Hahn H. Acquired resistance to Listeria monocytogenes is mediated by Lyt-2+ T cells independently of the influx of monocytes into granulomatous lesions. J Exp Med. 1989 Aug 1;170(2):589–594. doi: 10.1084/jem.170.2.589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Moore M. W., Carbone F. R., Bevan M. J. Introduction of soluble protein into the class I pathway of antigen processing and presentation. Cell. 1988 Sep 9;54(6):777–785. doi: 10.1016/s0092-8674(88)91043-4. [DOI] [PubMed] [Google Scholar]
  29. North R. J. Importance of thymus-derived lymphocytes in cell-mediated immunity to infection. Cell Immunol. 1973 Apr;7(1):166–176. doi: 10.1016/0008-8749(73)90193-7. [DOI] [PubMed] [Google Scholar]
  30. North R. J. The relative importance of blood monocytes and fixed macrophages to the expression of cell-mediated immunity to infection. J Exp Med. 1970 Sep 1;132(3):521–534. doi: 10.1084/jem.132.3.521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Pamer E. G., Harty J. T., Bevan M. J. Precise prediction of a dominant class I MHC-restricted epitope of Listeria monocytogenes. Nature. 1991 Oct 31;353(6347):852–855. doi: 10.1038/353852a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Portnoy D. A., Schreiber R. D., Connelly P., Tilney L. G. Gamma interferon limits access of Listeria monocytogenes to the macrophage cytoplasm. J Exp Med. 1989 Dec 1;170(6):2141–2146. doi: 10.1084/jem.170.6.2141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Poston R. M., Kurlander R. J. Analysis of the time course of IFN-gamma mRNA and protein production during primary murine listeriosis. The immune phase of bacterial elimination is not temporally linked to IFN production in vivo. J Immunol. 1991 Jun 15;146(12):4333–4337. [PubMed] [Google Scholar]
  34. Rammensee H. G., Schild H., Theopold U. Protein-specific cytotoxic T lymphocytes. Recognition of transfectants expressing intracellular, membrane-associated or secreted forms of beta-galactosidase. Immunogenetics. 1989;30(4):296–302. doi: 10.1007/BF02421334. [DOI] [PubMed] [Google Scholar]
  35. Romero P., Maryanski J. L., Corradin G., Nussenzweig R. S., Nussenzweig V., Zavala F. Cloned cytotoxic T cells recognize an epitope in the circumsporozoite protein and protect against malaria. Nature. 1989 Sep 28;341(6240):323–326. doi: 10.1038/341323a0. [DOI] [PubMed] [Google Scholar]
  36. Sasaki T., Mieno M., Udono H., Yamaguchi K., Usui T., Hara K., Shiku H., Nakayama E. Roles of CD4+ and CD8+ cells, and the effect of administration of recombinant murine interferon gamma in listerial infection. J Exp Med. 1990 Apr 1;171(4):1141–1154. doi: 10.1084/jem.171.4.1141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Schild H., Norda M., Deres K., Falk K., Rötzschke O., Wiesmüller K. H., Jung G., Rammensee H. G. Fine specificity of cytotoxic T lymphocytes primed in vivo either with virus or synthetic lipopeptide vaccine or primed in vitro with peptide. J Exp Med. 1991 Dec 1;174(6):1665–1668. doi: 10.1084/jem.174.6.1665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Van Bleek G. M., Nathenson S. G. Isolation of an endogenously processed immunodominant viral peptide from the class I H-2Kb molecule. Nature. 1990 Nov 15;348(6298):213–216. doi: 10.1038/348213a0. [DOI] [PubMed] [Google Scholar]
  39. Zinkernagel R. M., Althage A., Adler B., Blanden R. V., Davidson W. F., Kees U., Dunlop M. B., Shreffler D. C. H-2 restriction of cell-mediated immunity to an intracellular bacterium: effector T cells are specific for Listeria antigen in association with H-21 region-coded self-markers. J Exp Med. 1977 May 1;145(5):1353–1367. doi: 10.1084/jem.145.5.1353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. von Koenig C. H., Finger H., Hof H. Failure of killed Listeria monocytogenes vaccine to produce protective immunity. Nature. 1982 May 20;297(5863):233–234. doi: 10.1038/297233a0. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES