Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1997 Dec;65(12):5326–5329. doi: 10.1128/iai.65.12.5326-5329.1997

A nonamer peptide derived from Listeria monocytogenes metalloprotease is presented to cytolytic T lymphocytes.

D H Busch 1, H G Bouwer 1, D Hinrichs 1, E G Pamer 1
PMCID: PMC175766  PMID: 9393833

Abstract

Listeria monocytogenes is an intracellular bacterium that secretes proteins into the cytosol of infected macrophages. Major histocompatibility complex (MHC) class I molecules bind peptides that are generated by the degradation of bacterial proteins and present them to cytolytic T lymphocytes (CTL). In this study we have investigated CTL responses in L. monocytogenes-immunized mice to peptides that (i) derive from the L. monocytogenes proteins phosphatidylinositol-specific phospholipase C, lecithinase (most active on phosphatidylcholine), metalloprotease (Mpl), PrfA, and the ORF-A product and (ii) conform to the binding motif of the H2-Kd MHC class I molecule. We identified a nonamer peptide, Mpl 84-92, that is presented to L. monocytogenes-specific CTL by H2-Kd MHC class I molecules. Unlike other motif-conforming peptides derived from the secreted Mpl of L. monocytogenes, Mpl 84-92 is bound with high affinity by H2-Kd. Mpl 84-92 is the fourth L. monocytogenes-derived peptide found to be presented to CTL by the H2-Kd molecule during infection and demonstrates the importance of high-affinity interactions between antigenic peptides and MHC class I molecules for CTL priming.

Full Text

The Full Text of this article is available as a PDF (135.5 KB).

Selected References

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

  1. Bielecki J., Youngman P., Connelly P., Portnoy D. A. Bacillus subtilis expressing a haemolysin gene from Listeria monocytogenes can grow in mammalian cells. Nature. 1990 May 10;345(6271):175–176. doi: 10.1038/345175a0. [DOI] [PubMed] [Google Scholar]
  2. Bouwer H. G., Lindahl K. F., Baldridge J. R., Wagner C. R., Barry R. A., Hinrichs D. J. An H2-T MHC class Ib molecule presents Listeria monocytogenes-derived antigen to immune CD8+ cytotoxic T cells. J Immunol. 1994 Jun 1;152(11):5352–5360. [PubMed] [Google Scholar]
  3. Camilli A., Goldfine H., Portnoy D. A. Listeria monocytogenes mutants lacking phosphatidylinositol-specific phospholipase C are avirulent. J Exp Med. 1991 Mar 1;173(3):751–754. doi: 10.1084/jem.173.3.751. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Camilli A., Tilney L. G., Portnoy D. A. Dual roles of plcA in Listeria monocytogenes pathogenesis. Mol Microbiol. 1993 Apr;8(1):143–157. doi: 10.1111/j.1365-2958.1993.tb01211.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Domann E., Leimeister-Wächter M., Goebel W., Chakraborty T. Molecular cloning, sequencing, and identification of a metalloprotease gene from Listeria monocytogenes that is species specific and physically linked to the listeriolysin gene. Infect Immun. 1991 Jan;59(1):65–72. doi: 10.1128/iai.59.1.65-72.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Domann E., Wehland J., Rohde M., Pistor S., Hartl M., Goebel W., Leimeister-Wächter M., Wuenscher M., Chakraborty T. A novel bacterial virulence gene in Listeria monocytogenes required for host cell microfilament interaction with homology to the proline-rich region of vinculin. EMBO J. 1992 May;11(5):1981–1990. doi: 10.1002/j.1460-2075.1992.tb05252.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Gaillard J. L., Berche P., Sansonetti P. Transposon mutagenesis as a tool to study the role of hemolysin in the virulence of Listeria monocytogenes. Infect Immun. 1986 Apr;52(1):50–55. doi: 10.1128/iai.52.1.50-55.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gellin B. G., Broome C. V. Listeriosis. JAMA. 1989 Mar 3;261(9):1313–1320. [PubMed] [Google Scholar]
  10. Gulden P. H., Fischer P., 3rd, Sherman N. E., Wang W., Engelhard V. H., Shabanowitz J., Hunt D. F., Pamer E. G. A Listeria monocytogenes pentapeptide is presented to cytolytic T lymphocytes by the H2-M3 MHC class Ib molecule. Immunity. 1996 Jul;5(1):73–79. doi: 10.1016/s1074-7613(00)80311-8. [DOI] [PubMed] [Google Scholar]
  11. Harty J. T., Bevan M. J. CD8+ T cells specific for a single nonamer epitope of Listeria monocytogenes are protective in vivo. J Exp Med. 1992 Jun 1;175(6):1531–1538. doi: 10.1084/jem.175.6.1531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hess J., Gentschev I., Miko D., Welzel M., Ladel C., Goebel W., Kaufmann S. H. Superior efficacy of secreted over somatic antigen display in recombinant Salmonella vaccine induced protection against listeriosis. Proc Natl Acad Sci U S A. 1996 Feb 20;93(4):1458–1463. doi: 10.1073/pnas.93.4.1458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Horwitz M. A., Lee B. W., Dillon B. J., Harth G. Protective immunity against tuberculosis induced by vaccination with major extracellular proteins of Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1530–1534. doi: 10.1073/pnas.92.5.1530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kathariou S., Metz P., Hof H., Goebel W. Tn916-induced mutations in the hemolysin determinant affecting virulence of Listeria monocytogenes. J Bacteriol. 1987 Mar;169(3):1291–1297. doi: 10.1128/jb.169.3.1291-1297.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kocks C., Gouin E., Tabouret M., Berche P., Ohayon H., Cossart P. L. monocytogenes-induced actin assembly requires the actA gene product, a surface protein. Cell. 1992 Feb 7;68(3):521–531. doi: 10.1016/0092-8674(92)90188-i. [DOI] [PubMed] [Google Scholar]
  16. Leimeister-Wächter M., Haffner C., Domann E., Goebel W., Chakraborty T. Identification of a gene that positively regulates expression of listeriolysin, the major virulence factor of listeria monocytogenes. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8336–8340. doi: 10.1073/pnas.87.21.8336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lenz L. L., Dere B., Bevan M. J. Identification of an H2-M3-restricted Listeria epitope: implications for antigen presentation by M3. Immunity. 1996 Jul;5(1):63–72. doi: 10.1016/s1074-7613(00)80310-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Marquis H., Doshi V., Portnoy D. A. The broad-range phospholipase C and a metalloprotease mediate listeriolysin O-independent escape of Listeria monocytogenes from a primary vacuole in human epithelial cells. Infect Immun. 1995 Nov;63(11):4531–4534. doi: 10.1128/iai.63.11.4531-4534.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Pamer E. G. Direct sequence identification and kinetic analysis of an MHC class I-restricted Listeria monocytogenes CTL epitope. J Immunol. 1994 Jan 15;152(2):686–694. [PubMed] [Google Scholar]
  20. 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]
  21. Portnoy D. A., Chakraborty T., Goebel W., Cossart P. Molecular determinants of Listeria monocytogenes pathogenesis. Infect Immun. 1992 Apr;60(4):1263–1267. doi: 10.1128/iai.60.4.1263-1267.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Portnoy D. A., Jacks P. S., Hinrichs D. J. Role of hemolysin for the intracellular growth of Listeria monocytogenes. J Exp Med. 1988 Apr 1;167(4):1459–1471. doi: 10.1084/jem.167.4.1459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Poyart C., Abachin E., Razafimanantsoa I., Berche P. The zinc metalloprotease of Listeria monocytogenes is required for maturation of phosphatidylcholine phospholipase C: direct evidence obtained by gene complementation. Infect Immun. 1993 Apr;61(4):1576–1580. doi: 10.1128/iai.61.4.1576-1580.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sette A., Vitiello A., Reherman B., Fowler P., Nayersina R., Kast W. M., Melief C. J., Oseroff C., Yuan L., Ruppert J. The relationship between class I binding affinity and immunogenicity of potential cytotoxic T cell epitopes. J Immunol. 1994 Dec 15;153(12):5586–5592. [PubMed] [Google Scholar]
  25. Sijts A. J., Neisig A., Neefjes J., Pamer E. G. Two Listeria monocytogenes CTL epitopes are processed from the same antigen with different efficiencies. J Immunol. 1996 Jan 15;156(2):683–692. [PubMed] [Google Scholar]
  26. Smith G. A., Marquis H., Jones S., Johnston N. C., Portnoy D. A., Goldfine H. The two distinct phospholipases C of Listeria monocytogenes have overlapping roles in escape from a vacuole and cell-to-cell spread. Infect Immun. 1995 Nov;63(11):4231–4237. doi: 10.1128/iai.63.11.4231-4237.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Tilney L. G., Portnoy D. A. Actin filaments and the growth, movement, and spread of the intracellular bacterial parasite, Listeria monocytogenes. J Cell Biol. 1989 Oct;109(4 Pt 1):1597–1608. doi: 10.1083/jcb.109.4.1597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Vazquez-Boland J. A., Kocks C., Dramsi S., Ohayon H., Geoffroy C., Mengaud J., Cossart P. Nucleotide sequence of the lecithinase operon of Listeria monocytogenes and possible role of lecithinase in cell-to-cell spread. Infect Immun. 1992 Jan;60(1):219–230. doi: 10.1128/iai.60.1.219-230.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Wipke B. T., Jameson S. C., Bevan M. J., Pamer E. G. Variable binding affinities of listeriolysin O peptides for the H-2Kd class I molecule. Eur J Immunol. 1993 Aug;23(8):2005–2010. doi: 10.1002/eji.1830230842. [DOI] [PubMed] [Google Scholar]
  30. van der Burg S. H., Visseren M. J., Brandt R. M., Kast W. M., Melief C. J. Immunogenicity of peptides bound to MHC class I molecules depends on the MHC-peptide complex stability. J Immunol. 1996 May 1;156(9):3308–3314. [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES