Skip to main content
SpringerLink
Log in

MHC class I restricted T cell responses tolisteria monocytogenes, an intracellular bacterial pathogen

  • Published:
Immunologic Research Aims and scope Submit manuscript

Abstract

Studies of the murine immune response to infection with the intracellular bacterial pathogenListeria monocytogenes have provided a wealth of information about innate and acquired immune defenses in the setting of an infectious disease. Our studies have focused on the MHC class I restricted, CD8+ T cell responses of Balb/c mice toL. monocytogenes infection. Four peptides that derive from proteins thatL. monocytogenes secretes into the cytosol of infected cells are presented to cytotoxic T lymphocyte (CTL) by the H2-Kd major histocompatibility complex (MHC) class I molecule. We have found that bacterially secreted proteins are rapidly degraded in the host cell cytosol by proteasomes that utilize, at least in part, the N-end rule to determine the rate of degradation. The MHC class I antigen processing pathway is remarkably efficient at generating peptides that bind to MHC class I molecules. The magnitude of in vivo T cell responses, however, is influenced to only a small degree by the amount of antigen or the efficiency of antigen presentation. Measurements of in vivo T cell expansion followingL. monocytogenes infection indicate that differences in the sizes of peptide-specific T cell responses are more likely owing to differences in the repertoire of naive T cells than to differences in peptide presentation. This notion is supported by our additional finding that dominant T cell populations express a more diverse T cell receptor (TCR) repertoire than do subdominant T cell populations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Pamer EG: Immune response toListeria monocytogenes. Austin, R G Landes, 1997.

    Google Scholar 

  2. Gellin BG: Broome CV Listeriosis. JAMA 1989;261:1313–1320.

    Article  PubMed  CAS  Google Scholar 

  3. Mengaud J, Ohayon H, Gounon P, Mege RM, Cossart P: E-cadherin is the receptor for internalin, a surface protein required for entry of L monocytogenes into epithelial cells. Cell 1996;84:923–932.

    Article  PubMed  CAS  Google Scholar 

  4. Gaillard JL, Berche P, Frehel C, Gouin E, Cossart P: Entry ofL. monocytogenes into cells is mediated by internalin, a repeat protein reminiscent of surface antigens from Gram-positive cocci. Cell 1991;65:1127–1141.

    Article  PubMed  CAS  Google Scholar 

  5. Bielecki J, Youngman P, Connelly P, Portnoy DA:Bacillus subtilis expressing a haemolysin gene fromListeria monocytogenes can grow in mammalian cells. Nature 1990;345:175,176.

    Article  PubMed  CAS  Google Scholar 

  6. Tilney LG, Portnoy DA: Actin filaments and the growth, movement, and spread of the intracellular parasite,Listeria monocytogenes. J Cell Biol. 1989;109:1597–1608.

    Article  PubMed  CAS  Google Scholar 

  7. Domann E, Wehland J, Rohde M, Pistor S, Hartl M, et al.: A novel bacterial virulence gene inListeria monocytogenes required for host cell microfilament interaction with homology to the prolinerich region of vinculin. EMBO J 1992;11:1981–1990.

    PubMed  CAS  Google Scholar 

  8. 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;68:521–531.

    Article  PubMed  CAS  Google Scholar 

  9. Rogers HW, Callery MP, Deck B, Unanue ER:Listeria monocytogenes induces apoptosis of infected hepatocytes. J Immunol 1996; 156: 679–684.

    PubMed  CAS  Google Scholar 

  10. Villanueva MS, Beckers CJM, Pamer EG: Infection withListeria monocytogenes impairs sialic acid addition to host cell glycoproteins. J Exp Med 1994;62: 1881–1888.

    Google Scholar 

  11. Mackaness GB: Cellular resistance to infection. J Exp Med 1962; 116:381–406.

    Article  PubMed  CAS  Google Scholar 

  12. Miki K, Mackaness GB: The passive transfer of acquired resistance toListeria monocytogenes. J Exp Med 1964;120:93–103.

    Article  PubMed  CAS  Google Scholar 

  13. Unanue ER: Studies in listeriosis show the strong symbiosis between the innate cellular system and the T-cell response. Immunol Rev 1997;158:11–25.

    Article  PubMed  CAS  Google Scholar 

  14. Unanue ER: Why listeriosis? A perspective on cellular immunity to infection. Immunol Rev 1997; 158:5–11.

    Article  PubMed  CAS  Google Scholar 

  15. Unanue E: Inter-relationship among macrophages, natural killer cells and neutrophils in early stages ofListeria resistance. Curr Opinion Immunol 1997;9:35–43.

    Article  CAS  Google Scholar 

  16. Rogers HW, Unanue ER: Neutrophils are involved in acute, nonspecific resistance toListeria monocytogenes in mice. Infect Immun 1993;91:5090–5096.

    Google Scholar 

  17. Conlan JW, North RJ: Neutrophilmediated dissolution of infected host cells as a defense strategy against a facultative intracellular bacterium. J Exp Med 1991;174: 741–744.

    Article  PubMed  CAS  Google Scholar 

  18. Czuprynski CJ, Henson PM, Camp-bell PA: Enhanced accumulation of inflammatory neutrophils and macrophages mediated by transfer of T cells from mice immunized withListeria monocytogenes. J Immunol 1985;134:3449–3454.

    PubMed  CAS  Google Scholar 

  19. Conlan JW, North RJ: Neutrophils are essential for early anti-Listeria defense in the liver, but not in the spleen or peritoneal cavity, as revealed by a granulocyte-depleting monoclonal antibody. J Exp Med 1994;179:259–268.

    Article  PubMed  CAS  Google Scholar 

  20. Dunn PL, North RJ: Early gamma interferon production by natural killer cells is important in defense against murineListeriosis. Infect Immun 1991;59:2892–2900.

    PubMed  CAS  Google Scholar 

  21. Hiromatsu K, Yoshikai Y, Matsu-zaki G, Ohga S, Muramo K, Matsumo K, et al.: A protective role of γ/δ T cells in primary infection withListeria monocytogenes in mice. J Exp Med 1992; 175:49–56.

    Article  PubMed  CAS  Google Scholar 

  22. Bancroft GJ, Sheehan KC, Schrei-ber RD, Unanue ER: Tumor necrosis factor is involved in the T cell-independent pathway of macrophage activation in SCID mice. J Immunol 1989;143:127–130.

    PubMed  CAS  Google Scholar 

  23. Kaufmann SHE, Hug E, DeLibero G:Listeria monocytogenes reactive T lymphocyte clones with cytolytic activity against infected target cells. J Exp Med 1986; 164:363–368.

    Article  PubMed  CAS  Google Scholar 

  24. Harty JT, Schreiber RD, Bevan MJ: CD8 T cells can protect against an intracellular bacterium in an interferon gamma-independent fashion. Proc Natl Acad Sci USA 1992;89: 11,612–11,616.

    Article  CAS  Google Scholar 

  25. Harty JT, Bevan MJ: Specific immunity toListeria monocytogenes in the absence of INF gamma. Immunity 1995;3:109–118.

    Article  PubMed  CAS  Google Scholar 

  26. Ladel CH, Flesch IEF, Arnoldi J, Kaufmann SHE: Studies with MHC-deficient knock-out mice reveal impact of both MHC Iand MHC II-dependent T cell responses onListeria monocytogenes infection. J Immunol 1994; 153:3116–3122.

    PubMed  CAS  Google Scholar 

  27. Pamer EG, Harty JT, Bevan MJ: Precise prediction of a dominant class I MHC-restricted epitope ofListeria monocytogenes. Nature 1991;353:852–855.

    Article  PubMed  CAS  Google Scholar 

  28. Pamer EG: Direct sequence identification and kinetic analysis of an MHC class I-restrictedListeria monocytogenes CTL epitope. J Immunol 1994; 152:686–694.

    PubMed  CAS  Google Scholar 

  29. Wuenscher MD, Kohler S, Bubert A, Gerike U, Goebel W: Theiap gene ofListeria monocytogenes is essential for cell viability, and its gene product, p60, has bacteriolytic activity. J Bacteriol 1993; 175:3491–3501.

    PubMed  CAS  Google Scholar 

  30. Gentschev I, Sokolovic Z, Kohler S, Krohne G, Hof H, Wagner J, et al.: Identification of p60 antibodies in human sera and presentation of this Listerial antigen on the surface of attenuated Salmonellae by the HlyB-HlyD secretion system. Infect Immun 1992;60:5091–5098.

    PubMed  CAS  Google Scholar 

  31. Sijts AJAM, Neisig A, Neefjes J, Pamer EG: TwoListeria monocytogenes CTL epitopes are processed from the same antigen with different efficiencies. J Immunol 1996;156:685–692.

    CAS  Google Scholar 

  32. Harty JT, Pamer EG: CD8 T lymphocytes specific fo the secreted p60 antigen protect againstListeria monocytogenes infection. J Immunol 1995;154:4642–4650.

    PubMed  CAS  Google Scholar 

  33. Busch DH, Bouwer AGA, Hinrichs D, Pamer EG: A nonamer peptide derived fromListeria monocytogenes metalloprotease is presented to cytolytic T lymphocytes. Infect Immun 1997;65:5326–5329.

    PubMed  CAS  Google Scholar 

  34. Domann E, Leimeister-Wachter M, Goebel W, Chakraborty T: Molecular cloning, sequencing and identification of a metalloprotease gene fromListeria monocytogenes that is species specific and physically linked to the listeriolysin gene. Infect Immun 1991; 59:65–72.

    PubMed  CAS  Google Scholar 

  35. Marquis H, Doshi V, Portnoy DA: The broad-range phospholipase C and a metalloprotease mediate listeriolysin O-independent escape ofListeria monocytogenes from a primary vacuole in human epithelial cells. Infect Immun 1995;63: 4531–4534.

    PubMed  CAS  Google Scholar 

  36. Villanueva MS, Fischer P, Feen K, Pamer EG: Efficiency of antigen processing: a quantitative analysis. Immunity 1994;1:479–489.

    Article  PubMed  CAS  Google Scholar 

  37. Hess J, Gentschev I, Miko D, Welzel M, Ladel C, Goebel W, et al.: Superior efficacy of secreted over somatic antigen display in recombinant Salmonella vaccine induced protection against listeriosis. Proc Natl Acad Sci USA 1996;93:1458–1463.

    Article  PubMed  CAS  Google Scholar 

  38. Hess J, Dietrich G, Gentschev I, Miko D, Goebel W, Kaufmann SHE: Protection against murine listeriosis by an attenuated recombinant Salmonella typhimurium vaccine strain that secretes the naturally somatic antigen superoxide dismutase. Infect Immun 1997;65:1286–1292.

    PubMed  CAS  Google Scholar 

  39. Shen H, Miller JF, Fan X, Kolwyck D, Ahmed R, Harty JT: Compartmentalization of bacterial antigens: differential effects on priming of CD8 T cells and protective immunity. Cell 1998;92:535–545.

    Article  PubMed  CAS  Google Scholar 

  40. Pamer EG: Cell mediated immunity: The role of bacterial protein secretion. Curr Biol 1998;8:457–460.

    Article  Google Scholar 

  41. Sijts AJA, Pamer EG: Enhanced intracellular dissociation of major histocompatibility complex class I-associated peptides: a mechanism for optimizing the spectrum of cell surface-presented cytotoxic tT lymphocyte epitopes. J Exp Med 1997;185:1403–1411.

    Article  PubMed  CAS  Google Scholar 

  42. Levitsky V, Zhang QJ, Levitskaya J, Kurilla MG, Masucci MG: Natural variants of the immunodominant HLA A 11-restricted CTL epitope of the EBV nuclear antigen-4 are nonimmunogenic due to intracellular dissociation from MHC class I:peptide complexes. J Immunol 1997;159: 5383–5390.

    PubMed  CAS  Google Scholar 

  43. Villanueva MS, Sijts AJAM, Pamer EG: Listeriolysin is processed efficiently into an MHC class I-associated epitope inListeria monocytogenes-infected cells. J Immunol 1995;155:5227–5233.

    PubMed  CAS  Google Scholar 

  44. Hochstrasser M: Ubiquitin-dependent protein degradation. Annu Rev Genet 1997;30:405–439.

    Article  Google Scholar 

  45. Ciechanover A: The ubiquitinproteasome proteolytic pathway. Cell 1994;79:13–21.

    Article  PubMed  CAS  Google Scholar 

  46. Sijts AJAM, Pilip I, Pamer EG: TheListeria monocytogenes p60 protein is an N-end rule substrate in the cytosol of infected cells: implications for MHC class I antigen processing of bacterial proteins. J Biol Chem 1997;272: 19,261–19,268.

    Article  CAS  Google Scholar 

  47. Sijts AJAM, Villanueva MS, Pamer EG: CTL epitope generation is tightly linked to cellular proteolysis of aListeria monocytogenes antigen. J Immunol 1996; 156:1497–1503.

    PubMed  CAS  Google Scholar 

  48. Miyahira Y, Murata K. Rodriguez D, Rodriguez J, Esteban M, Rodriguez M, et al.: Quantification of antigen specific CD8+ T cells using an ELISPOT assay. J Immunol Methods 1995; 181:45–54.

    Article  PubMed  CAS  Google Scholar 

  49. Vijh S, Pamer EG: Immunodominant and subdominant CTL responses toListeria monocytogenes infection. J Immunol 1997; 158:3366–3371.

    PubMed  CAS  Google Scholar 

  50. Busch DH, Pamer EG: MHC class I/peptide stability: implications for immunodominance, in vitro proliferation and diversity of responding CTL J Immunol 1998; 160:4441–4448.

    PubMed  CAS  Google Scholar 

  51. Vijh S, Pilip IM, Pamer EG: Effect of antigen processing efficiency on in vivo T cell response magnitudes. J Immunol 1998;160: 3971–3977.

    PubMed  CAS  Google Scholar 

  52. Vijh S, Pilip IM, Pamer EG: Noncompetitive expansion of CTL specific for different antigens during bacterial infection. Infect Immun 1998;67:1303–1309.

    Google Scholar 

  53. Altman JD, Moss PAH, Goulder PJR, Barouch DH, McHeyzer- Williams, Bell JI, et al.: Phenotypic analysis of antigen specific T lymphocytes. Science 1996; 274:94–96.

    Article  PubMed  CAS  Google Scholar 

  54. Busch DH, Pilip IM, Vijh S, Pamer EG: Coordinate regulation of complex T cell populations responding to bacterial infection. Immunity 1998;8:353–362.

    Article  PubMed  CAS  Google Scholar 

  55. Busch DH, Pilip I, Pamer EG: Evolution of a complex T cell receptor repertoire during primary and recall bacterial infection. J Exp Med 1998;188:61–70.

    Article  PubMed  CAS  Google Scholar 

  56. Sourdive DJD, Murali-Krishna K, Altman JD, Zajac AJ, Whitmire JK, Pannetier C, et al.: Conserved T cell receptor repertoire in primary and memory CD8 T cell responses to acute viral infection. J Exp Med 1998;188:71–82.

    Article  PubMed  CAS  Google Scholar 

  57. Callan MFC, Annels N, Steven N, Tan L, Wilson J, McMichael AJ, et al.: T cell selection during the evolution of CD8+ T cell memory in vivo. Eur. J Immunol 1998; 28:4382–4390.

    Article  PubMed  CAS  Google Scholar 

  58. Busch DH, Pamer EG: T cell affinity maturation by selective expansion following infection. J Exp Med 1999;189:701–709.

    Article  PubMed  CAS  Google Scholar 

  59. Kaufmann SHE, Rodewald HR, Hug E, Libero GD: ClonedListeria monocytogenes specific non-MHC-restricted Lyt-2+ T cells with cytolytic and protective activity. J Immunol 1988;140: 3173–3179.

    PubMed  CAS  Google Scholar 

  60. Lukacs K, Kurlander RJ: MHC-unrestricted transfer of antilisterial immunity by freshly isolated immune CD8 spleen cells. J Immunol 1989;143:3731–3736.

    PubMed  CAS  Google Scholar 

  61. Kurlander RJ, Shawar SM, Brown ML, Rich RR: Specialized role for a murine class I-b MHC molecule in prokaryotic host defenses. Science 1992;257:678–679.

    Article  PubMed  CAS  Google Scholar 

  62. Pamer EG, Wang CR, Flaherty L, Lindahl KF, Bevan MJ: H2-M3 presents aListeria monocytogenes peptide to cytotoxic T lymphocytes. Cell 1992;70:215–223.

    Article  PubMed  CAS  Google Scholar 

  63. Shawar SM, Cook RG, Rodgers JR, Rich RR: Specialized functions of MHC class I molecules. I An N-formyl peptide receptor is required for construction of the class I antigen Mta. J Exp Med 1990;171:897–912.

    Article  PubMed  CAS  Google Scholar 

  64. Loveland BE, Wang CR, Yone-kawa H, Hermel E, Lindahl KF: Maternally transmitted histocompatibility antigen of mice: a hydrophobic peptide of a mitochondrially encoded protein. Cell 1990;60: 971–980.

    Article  PubMed  CAS  Google Scholar 

  65. Gulden PH, Fischer P, Sherman NE, Wang W, Engelhard V, Shabano-witz J, et al.: AListeria monocytogenes pentapeptide is presented to cytolytic T lymphocytes by the H2-M3 MHC class Ib molecule. Immunity 1996;5:73–79.

    Article  PubMed  CAS  Google Scholar 

  66. Lenz LL, Dere B, Bevan MJ: Identification of an H2-M3-restricted Listeria epitope: Implications for antigen presentation by M3. Immunity 1996;5:63–72.

    Article  PubMed  CAS  Google Scholar 

  67. Princiotta MF, Lenz LL, Bevan MJ, Staerz UD: H2-M3 restricted presentation of a Listeria-derived leader peptide. J Exp Med 1998; 187:1711–1720.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Sections of Infectious Diseases and Immunobiology, Yale University School of Medicine, 06520, New Haven, CT

    Alyce Finelli, Kristen M. Kerksiek, S. Elise Allen, Natalia Marshall, Roberto Mercado, Ingrid Pilip, Dirk H. Busch & Eric G. Pamer

  2. Section of Infectious Diseases LCI 803, 333 Cedar St., 06520-8022, New Haven, CT

    Eric G. Pamer

Authors
  1. Alyce Finelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kristen M. Kerksiek
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Elise Allen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Natalia Marshall
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Roberto Mercado
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ingrid Pilip
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Dirk H. Busch
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Eric G. Pamer
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Finelli, A., Kerksiek, K.M., Allen, S.E. et al. MHC class I restricted T cell responses tolisteria monocytogenes, an intracellular bacterial pathogen. Immunol Res 19, 211–223 (1999). https://doi.org/10.1007/BF02786489

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02786489

Key Words

Search

Navigation