1887

Abstract

The identification of all antigenic peptides encoded by a pathogen, its T cell ‘immunome’, is a research aim for rational vaccine design. Screening of proteome-spanning peptide libraries or computational prediction is used to identify antigenic peptides recognized by CD8 T cells. Based on their high coding capacity, cytomegaloviruses (CMVs) could specify numerous antigenic peptides. Yet, current evidence indicates that the memory CD8 T cell response in a given haplotype is actually focused on a few viral proteins. CMVs actively interfere with antigen processing and presentation by the expression of immune evasion proteins. In the case of murine CMV (mCMV), these proteins are effectual in the early (E) phase of the virus replication cycle and should thus preclude the presentation of peptides derived from E proteins. Notably, the gene is here added to a growing list of mCMV E genes that encode antigenic peptides in spite of the E phase immune evasion strategies of the virus.

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2002-02-01
2024-03-29
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References

  1. Alterio de Goss M., Holtappels R., Steffens H.-P., Podlech J., Angele P., Dreher L., Thomas D., Reddehase M. J. 1998; Control of cytomegalovirus in bone marrow transplantation chimeras lacking the prevailing antigen-presenting molecule in recipient tissues rests primarily on recipient-derived CD8 T cells. Journal of Virology 72:7733–7744
    [Google Scholar]
  2. Bresnahan W. A., Shenk T. 2000; A subset of viral transcripts packaged within human cytomegalovirus particles. Science 288:2373–2376
    [Google Scholar]
  3. Chapman T. L., Heikeman A. P., Bjorkman P. J. 1999; The inhibitory receptor LIR-1 uses a common binding interaction to recognize class I MHC molecules and the viral homolog UL18. Immunity 11:603–613
    [Google Scholar]
  4. Cosman D., Fanger N., Borges L. 1999; Human cytomegalovirus, MHC class I and inhibitory signalling receptors: more questions than answers. Immunological Reviews 168:177–185
    [Google Scholar]
  5. Cranmer L. D., Clark C. L., Morello C. S., Farrell H. E., Rawlinson W. D., Spector D. H. 1996; Identification, analysis, and evolutionary relationships of the putative murine cytomegalovirus homologs of the human cytomegalovirus UL82 (pp71) and UL83 (pp65) matrix phosphoproteins. Journal of Virology 70:7929–7939
    [Google Scholar]
  6. Del Val M., Münch K., Reddehase M. J., Koszinowski U. H. 1989; Presentation of CMV immediate-early antigen to cytolytic T lymphocytes is selectively prevented by viral genes expressed in the early phase. Cell 58:305–315
    [Google Scholar]
  7. Del Val M., Hengel H., Hacker H., Hartlaub U., Ruppert T., Lucin P., Koszinowski U. H. 1992; Cytomegalovirus prevents antigen presentation by blocking the transport of peptide-loaded major histocompatibility complex class I molecules into the medial-Golgi compartment. Journal of Experimental Medicine 176:729–738
    [Google Scholar]
  8. Ebeling A., Keil G. M., Knust E., Koszinowski U. H. 1983; Molecular cloning and physical mapping of murine cytomegalovirus DNA. Journal of Virology 47:421–433
    [Google Scholar]
  9. Hengel H., Brune W., Koszinowski U. H. 1998; Immune evasion by cytomegalovirus–survival strategies of a highly adapted opportunist. Trends in Microbiology 6:190–197
    [Google Scholar]
  10. Hengel H., Reusch U., Gutermann A., Ziegler H., Jonjic S., Lucin P., Koszinowski U. H. 1999; Cytomegaloviral control of MHC class I function in the mouse. Immunological Reviews 168:167–176
    [Google Scholar]
  11. Holtappels R., Podlech J., Geginat G., Steffens H.-P., Thomas D., Reddehase M. J. 1998; Control of murine cytomegalovirus in the lungs: relative but not absolute immunodominance of the immediate-early 1 nonapeptide during the antiviral cytolytic T-lymphocyte response in pulmonary infiltrates. Journal of Virology 72:7201–7212
    [Google Scholar]
  12. Holtappels R., Thomas D., Podlech J., Geginat G., Steffens H.-P., Reddehase M. J. 2000a; The putative natural killer decoy early gene m04 (gp34) of murine cytomegalovirus encodes an antigenic peptide recognized by protective antiviral CD8 T cells. Journal of Virology 74:1871–1884
    [Google Scholar]
  13. Holtappels R., Thomas D., Reddehase M. J. 2000b; Identification of a Kd-restricted antigenic peptide encoded by murine cytomegalovirus early gene M84 . Journal of General Virology 81:3037–3042
    [Google Scholar]
  14. Holtappels R., Pahl-Seibert M.-F., Thomas D., Reddehase M. J. 2000c; Enrichment of immediate-early 1 ( m123 /pp89) peptide-specific CD8 T cells in a pulmonary CD62Llo memory-effector cell pool during latent murine cytomegalovirus infection of the lungs. Journal of Virology 74:11495–11503
    [Google Scholar]
  15. Holtappels R., Podlech J., Grzimek N. K. A., Thomas D., Pahl-Seibert M.-F., Reddehase M. J. 2001; Experimental preemptive immunotherapy of murine cytomegalovirus disease with CD8 T-cell lines specific for ppM83 and pM84, the two homologues of human cytomegalovirus tegument protein ppUL83 (pp65). Journal of Virology 75:6584–6600
    [Google Scholar]
  16. Holtappels R., Thomas D., Podlech J., Reddehase M. J. 2002; Two antigenic peptides from genes m123 and m164 of murine cytomegalovirus quantitatively dominate CD8 T-cell memory in the H-2 d haplotype. Journal of Virology 76:151–164
    [Google Scholar]
  17. Kleijnen M. F., Huppa J. B., Lucin P., Mukherjee S., Farrell H. E., Campbell A. E., Koszinowski U. H., Hill A. B., Ploegh H. L. 1997; A mouse cytomegalovirus glycoprotein, gp34, forms a complex with folded class I MHC molecules in the ER which is not retained but is transported to the cell surface. EMBO Journal 16:685–694
    [Google Scholar]
  18. Lie W.-R., Myers N. B., Connolly J. M., Gorka J., Lee D. R., Hansen T. H. 1991; The specific binding of peptide ligand to Ld class I major histocompatibility complex molecules determines their antigenic structure. Journal of Experimental Medicine 173:449–459
    [Google Scholar]
  19. McNally J. M., Zarozinski C. C., Lin M. Y., Brehm M. A., Chen H. D., Welsh R. M. 2001; Attrition of bystander CD8 T cells during virus-induced T-cell and interferon responses. Journal of Virology 75:5965–5976
    [Google Scholar]
  20. Morello C. S., Cranmer L. D., Spector D. H. 1999; In vivo replication, latency, and immunogenicity of murine cytomegalovirus mutants with deletions in the M83 and M84 genes, the putative homologs of human cytomegalovirus pp65 (UL83. Journal of Virology 73:7678–7693
    [Google Scholar]
  21. Morello C. S., Cranmer L. D., Spector D. H. 2000; Suppression of murine cytomegalovirus (MCMV) replication with a DNA vaccine encoding MCMV M84 (a homolog of human cytomegalovirus pp65. Journal of Virology 74:3696–3708
    [Google Scholar]
  22. Rammensee H.-G., Bachmann J., Stevanovic S. 1997 MHC ligands and peptide motifs. Molecular Biology Intelligence Unit Landes Bioscience, Austin, TX, USA:
    [Google Scholar]
  23. Rawlinson W. D., Farrell H. E., Barrell B. G. 1996; Analysis of the complete DNA sequence of murine cytomegalovirus. Journal of Virology 70:8833–8849
    [Google Scholar]
  24. Reddehase M. J. 2000; The immunogenicity of human and murine cytomegaloviruses. Current Opinion in Immunology 12: 390–396, 738
    [Google Scholar]
  25. Reddehase M. J., Fibi M. R., Keil G. M., Koszinowski U. H. 1986; Late-phase expression of a murine cytomegalovirus immediate-early antigen recognized by cytolytic T lymphocytes. Journal of Virology 60:1125–1129
    [Google Scholar]
  26. Reddehase M. J., Rothbard J. B., Koszinowski U. H. 1989; A pentapeptide as minimal antigenic determinant for MHC class I-restricted T lymphocytes. Nature 337:651–653
    [Google Scholar]
  27. Reddehase M. J., Balthesen M., Rapp M., Jonjic S., Pavic I., Koszinowski U. H. 1994; The conditions of primary infection define the load of latent viral genome in organs and the risk of recurrent cytomegalovirus disease. Journal of Experimental Medicine 179:185–193
    [Google Scholar]
  28. Reusch U., Muranyi W., Lucin P., Burgert H. G., Hengel H., Koszinowski U. H. 1999; A cytomegalovirus glycoprotein re-routes MHC class I complexes to lysosomes for degradation. EMBO Journal 18:1081–1091
    [Google Scholar]
  29. Reyburn H. T., Mandelboim O., Vales-Gomez M., Davis D. M., Pazmany L., Strominger J. L. 1997; The class I MHC homologue of human cytomegalovirus inhibits attack by natural killer cells. Nature 386:514–517
    [Google Scholar]
  30. Rost B., Fariselli P., Casadio R. 1996; Topology prediction for helical transmembrane proteins at 86% accuracy. Protein Science 5:1704–1718
    [Google Scholar]
  31. Tough D. F., Borrow P., Sprent J. 1996; Induction of bystander T cell proliferation by viruses and type I interferon in vivo . Science 272:1947–1950
    [Google Scholar]
  32. Ziegler H., Thäle R., Lucin P., Muranyi W., Flohr T., Hengel H., Farrell H., Rawlinson W., Koszinowski U. H. 1997; A mouse cytomegalovirus glycoprotein retains MHC class I complexes in the ERGIC/cis-Golgi compartments. Immunity 6:57–66
    [Google Scholar]
  33. Ziegler H., Muranyi W., Burgert H. G., Kremmer E., Koszinowski U. H. 2000; The luminal part of the murine cytomegalovirus glycoprotein gp40 catalyses the retention of MHC class I molecules. EMBO Journal 19:870–881
    [Google Scholar]
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