1887

Abstract

CD8 cytotoxic T cell (CTL) clones with specificity for defined minor and major histocompatibility (H) antigens were used to monitor antigen presentation in human cytomegalovirus (HCMV)-infected skin fibroblasts. At the immediate early stage of virus replication antigen presentation was intact, but was abolished during the early and late phase. Lack of CTL recognition was not selective for certain antigens but was associated with decreased steady state levels of nascent MHC class I complexes and unassembled MHC class I heavy chains, whereas free β-microglobulin remained abundant. HCMV also affected the stability of both immature endoglycosidase H (Endo H)-sensitive and mature Endo H-resistant MHC class I molecules, suggesting that the virus interferes with antigen presentation at more than one step during maturation of the MHC class I complex. The action of interferon- (IFN-) and tumour necrosis factor- (TNF-) lifted the block of MHC class I complex formation by stimulating synthesis, assembly and stability of MHC class I molecules. This resulted in restored antigen presentation provided that cells were exposed to the factors before HCMV infection. Because few MHC molecules suffice for CTL recognition these cytokines compensated for the negative viral effect on the antigen presentation function. Nevertheless, the viral interference with MHC class I complex formation was still active. The data imply that specific cytokines limit the immune evasion potential of HCMV from CD8 T lymphocyte control.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-76-12-2987
1995-12-01
2024-04-23
Loading full text...

Full text loading...

/deliver/fulltext/jgv/76/12/JV0760122987.html?itemId=/content/journal/jgv/10.1099/0022-1317-76-12-2987&mimeType=html&fmt=ahah

References

  1. Barnes P., Grundy J. E. 1992; Down-regulation of the class I HLA heterodimer and ß 2-microglobulin on the surface of cells infected with cytomegalovirus. Journal of General Virology 73:2395–2403
    [Google Scholar]
  2. Beersma M. F. C., Bijlmakers M. J. E., Ploegh H. L. 1993; Human cytomegalovirus down-regulates HLA class I expression by reducing the stability of class I H chains. Journal of Immunology 151:4455–4464
    [Google Scholar]
  3. Borysiewicz L. K., Hickling J. K., Graham S., Sinclair J., Cranage M. P., Smith G. L., Sissons J. G. P. 1988; Human cytomegalovirus-specific cytotoxic T cells. Relative frequency of stage-specific CTL recognizing the 72-kD immediate early protein and glycoprotein B expressed by recombinant vaccinia viruses. Journal of Experimental Medicine 168:919–931
    [Google Scholar]
  4. Browne H., Smith G., Beck S., Minson T. 1990; A complex between the MHC class I homologue encoded by human cytomegalovirus and ß 2 microglobulin. Nature 347:770–772
    [Google Scholar]
  5. Bushkin Y., Posnett D. N., Pernis B., Wang C. Y. 1986; A new HLA-linked T cell membrane molecule related to the beta chain of the clonotypic receptor associated with T3. Journal of Experimental Medicine 164:458–473
    [Google Scholar]
  6. Collins T., Lapierre L. A., Fiers W., Strominger J. L., Pober J. S. 1986; Recombinant human tumor necrosis factor increases mRNA levels and surface expression of HLA-A, B antigens in vascular endothelial cells and dermal fibroblasts in vitro. Proceedings of the National Academy of Sciences, USA 83:446–450
    [Google Scholar]
  7. De Bueger M., Barker A., van Rood J. J., van der Woude F., Goulmy E. 1992; Tissue distribution of human minor histocompatibility antigens. Ubiquitous versus restricted tissue distribution indicates heterogeneity among human cytotoxic T lymphocyte-defined non-MHC antigens. Journal of Immunology 149:1788–1794
    [Google Scholar]
  8. Del Val M., Munch K., Reddehase M. J., Koszinowski U. H. 1989; Presentation of cytomegalovirus immediate-early antigens to cytolytic T lymphocytes is selectively blocked by viral genes expressed in the early phase. Cell 58:305–315
    [Google Scholar]
  9. Del Val M., Hengel H., Hacker H., Hartlaub U., Ruppert T., Lucin P., Koszinowski U. H. 1992; Cytomegalovirus prevents antigen presentation blocking the transport of peptide-loaded major histocompatibility complex class I molecules into the medial-Golgi compartment. Journal of Experimental Medicine 172:729–738
    [Google Scholar]
  10. Downes K., Grundy J. E. 1993; Upregulation of LFA-3 and ICAM-1 on the surface of fibroblasts infected with cytomegalovirus. Immunology 78:405–412
    [Google Scholar]
  11. Drew W. L., Mintz L. 1984; Cytomegalovirus infection in healthy and immune-deficient homosexual men. In The Acquired Immune Deficiency Syndrome and Infections of Homosexual Men pp 117–123 Edited by Ma P., Armstrong D. New York: Yorke Medical Books;
    [Google Scholar]
  12. Früh K., Ahn K., Djaballah H., Sempe P., van Endert P. M., Tampe R., Peterson P. A., Young Yang . 1995; A viral inhibitor of peptide transporters for antigen presentation. Nature 375:415–118
    [Google Scholar]
  13. Gilbert M. G., Riddell S. R., Li C. R., Greenberg P. D. 1993; Selective interference with class I major histocompatibility complex presentation of the major immediate-early protein following infection with human cytomegalovirus. Journal of Virology 67:3461–3469
    [Google Scholar]
  14. Gleaves C. A., Smith T. F., Shuster E. A., Pearson G. R. 1984; Rapid detection of cytomegalovirus in MRC-5 cells inoculated with urine specimens by using low speed centrifugation and monoclonal antibody to an early antigen. Journal of Clinical Microbiology 19:917–919
    [Google Scholar]
  15. Goulmy E. 1988; Minor histocompatibility antigens and their role in transplantation. In Transplant Review pp 29–54 Edited by Morris P. J., Tilney N. L. Location: Saunders Co;
    [Google Scholar]
  16. Goulmy E., Termiitelen A., Bradley B. A., Van Rood J. J. 1977; Y-antigen killing by T cells of women is restricted by HLA. Nature 266:544–545
    [Google Scholar]
  17. Hengel H., Lucin P., Jonjic S., Ruppert T., Koszinowski U. H. 1994; Restoration of cytomegalovirus antigen presentation by gamma interferon combats viral escape. Journal of Virology 68:289–297
    [Google Scholar]
  18. Hill A., Jugovic P., York I., Russ G., Bennink J., Yewdell J., Ploegh H., Johnson D. 1995; Herpes simplex virus turns off the TAP to evade host immunity. Nature 375:411–415
    [Google Scholar]
  19. Ho M. 1982; Human cytomegalovirus infections in immunosuppressed patients. In Cytomegalovirus, Biology and Infection: Current Topics in Infectious Disease pp 171–204 Edited by Greenough W. B., Merigan T. C. New York: Plenum Press;
    [Google Scholar]
  20. Hsu V. W., Yuan L. C., Nuchtern J. G., Lippincott-Schwartz J., Hammerling G. J., Klausner R. D. 1991; A recycling pathway between the endoplasmic reticulum and the Golgi apparatus for retention of unassembled MHC class I molecules. Nature 352:441–144
    [Google Scholar]
  21. Kelly A., Powis S. H., Glynne R., Radley E., Beck S., Trowsdale J. 1991; Second proteasomerelated gene in the human MHC class II region. Nature 353:667–668
    [Google Scholar]
  22. Klar D., Hämmerling G. J. 1989; Induction of assembly of MHC class I heavy chains with ß2-microglobulin by interferon-γ. EMBO Journal 8:475–481
    [Google Scholar]
  23. Kobata A. 1979; Use of endo- and exoglycosidases for structural studies of glycoconjugates. Annals of Biochemistry 100:1–14
    [Google Scholar]
  24. Kornfeld R., Kornfeld S. 1985; Assembly of asparagine-linked oligosaccharides. Annual Review of Biochemistry 54:631–664
    [Google Scholar]
  25. Krammer P., ten Kate F. W. J., Bijnen A. B., Jeekel J., Welmar W. 1984; Recombinant leukocyte interferon A induces steroid-resistant acute vascular rejection episodes in renal transplant recipients. Lancet i:989–990
    [Google Scholar]
  26. Kuzushima K., Isobe K. I., Morishima T., Takatsuki A., Nakashima I. 1990; Inhibitory effect of herpes simplex virus infection to target cells on recognition of minor histocompatibility antigens by cytotoxic T lymphocytes. Journal of Immunology 144:4536–4540
    [Google Scholar]
  27. Kvist S., Hamann U. 1990; A nucleoprotein peptide of inflenza A virus stimulates assembly of HLA-B27 class I heavy chains and ß 2-microglobulin translated in vitro. Nature 348:446–448
    [Google Scholar]
  28. Levy F., Gabathuler R., Larsson R., Kvist S. 1991; ATP is required for in vitro assembly of MHC class I antigens but not for transfer of peptides across the ER membrane. Cell 67:265–274
    [Google Scholar]
  29. Lie W.-R., Myers N. B., Gorka J., Rubocki R. J., Conolly J. M., Hansen T. H. 1990; Peptide ligand induced conformation and surface expression of the Ld class I MHC molecule. Nature 344:439–141
    [Google Scholar]
  30. Lucin P., Jonjic S., Messerle M., Polic B., Hengel H., Koszinowski U. H. 1994; Late phase inhibition of murine cytomegalovirus replication by synergistic action of interferon-gamma and tumour necrosis factor. Journal of General Virology 75:101–110
    [Google Scholar]
  31. Martinez C. K., Monaco J. J. 1991; Homology of proteasome subunits to a major histocompatibility complex-linked LMP gene. Nature 353:664–667
    [Google Scholar]
  32. Meyers J. D., Flournoy N., Thomas E. D. 1986; Risk factor for cytomegalovirus infection after human marrow transplantation. Journal of Infectious Diseases 153:478–488
    [Google Scholar]
  33. Miller W., Flynn P., McCullough J., Balfour H. H., Goldman A., Haake R., McGlave P., Ramsey N., Kersay J. 1986; Cytomegalovirus infection after bone marrow transplantation: an association with acute graft-versus-host disease. Blood 67:1162–1167
    [Google Scholar]
  34. Ortmann B., Androlewicz M. J., Cresswell P. 1994; MHC class I/ß 2-microglobulin complexes associate with TAP transporters before peptide binding. Nature 368:864–867
    [Google Scholar]
  35. Ortiz-Navarrete V., Seelig A., Gernold M., Frentzel S., Kloetzel P. M., Hammerling G. J. 1991; Subunit of the 20S proteasome (multicatalytic proteinase) encoded by the major histocompatibility complex. Nature 353:662–664
    [Google Scholar]
  36. Pestka S., Langer J. A., Zoon K. C., Samuel C. E. 1987; Interferons and their actions. Annual Review of Biochemistry 56:727–777
    [Google Scholar]
  37. Pfitzenmaier K., Scheurich P., Schluter C., Kronke M. 1987; Tumor necrosis factor enhances HLA-A, B, C and HLA-DR gene expression in human tumor cells. Journal of Immunology 138:975–980
    [Google Scholar]
  38. Powis S., Townsend A. R. M., Deverson E. V., Bastin J., Butcher G. W., Howard J. C. 1991; Restoration of antigen presentation to the mutant cell line RMA-S by an MHC-linked transporter. Nature 354:528–531
    [Google Scholar]
  39. Rajagopalan S., Brenner M. B. 1994; Calnexin retains unassembled major histocompatibility complex class I free heavy chains in the endoplasmic reticulum. Journal of Experimental Medicine 180:407–412
    [Google Scholar]
  40. Reddehase M. J., Mutter W., Munch K., Buhring H. J., Koszinowski U. H. 1987; CD8-positive T lymphocytes specific for murine cytomegalovirus immediate-early antigens mediate protective immunity. Journal of Virology 61:3102–3108
    [Google Scholar]
  41. Koszinowski U. H. 1987; CD8-positive T lymphocytes specific for murine cytomegalovirus immediate-early antigens mediate protective immunity. Journal of Virology 61:3102–3108
    [Google Scholar]
  42. Riddell S., Watanabe K., Goodrich J., Li C. R., Agha M., Greenberg P. 1992; Restoration of viral immunity in immuno-deficient humans by the adoptive transfer of T cell clones. Science 257:238–241
    [Google Scholar]
  43. Rötzschke O., Falk K., Deres K., Schild H., Norda M., Metzger J., Jung G., Rammensee H. G. 1990; Isolation and analysis of naturally processed viral peptides as recognized by cytotoxic T cells. Nature 348:252–254
    [Google Scholar]
  44. Rubin R. H. 1990; Impact of cytomegalovirus infection on organ transplant recipients. Reviews of Infectious Diseases 12: (Suppl. 7) S754.
    [Google Scholar]
  45. Sibille C., Gould K., Hammerling G., Townsend A. 1992; A defect in the presentation of intracellular viral antigens is restored by interferon-γ in cell lines with impaired major histocompatibility complex class I assembly. European Journal of Immunology 22:433–140
    [Google Scholar]
  46. Spies T., Bresnahon M., Bahram S., Arnold D., Blanck G., Mellus E., Pious D., DeMars R. 1990; A gene in the human major histocompatibility complex class II region controlling the class I antigen presentation pathway. Nature 348:744–747
    [Google Scholar]
  47. Suh W.-K., Cohen-Doyle M. F., Früh K., Wang K., Peterson P. A., Williams D. B. 1994; Interaction of MHC class I molecules with the transporter associated with antigen processing. Science 264:1322–1326
    [Google Scholar]
  48. Thäle R., Szepan U., Hengel H., Geginat G., Lucin P., Koszinowski U. 1995; Identification of the mouse cytomegalovirus genomic region affecting MHC class I molecule transport. Journal of Virology (in press)
    [Google Scholar]
  49. Townsend A., Bodmer H. 1989; Antigen recognition by class I-restricted T lymphocytes. Annual Review of Immunology 7:601–624
    [Google Scholar]
  50. Townsend A., Elliott T., Cerundolo V., Foster L., Barber B., Tse A. 1990; Assembly of MHC class I molecules analyzed in vitro. Cell 62:285–295
    [Google Scholar]
  51. Van Els C. A. C. M., D’Amaro J., Pool J., Barker A., Van den Elsen P. J., Van Rood J. J., Goulmy E. 1992; Immunogenetics of human minor histocompatibility antigens: their polymorphism and immunodominance. Immunogenetics 35:161–165
    [Google Scholar]
  52. Warren A. P., Ducroq D. H., Lehner P. J., Borysiewicz L. K. 1994; Human-cytomegalovirus-infected cells have unstable assembly of major histocompatibility complex class I complexes and are resistant to lysis by cytotoxic T lymphocytes. Journal of Virology 68:2822–2829
    [Google Scholar]
  53. Wiedbrauk D. L., Johnston S. L. G. 1992 Manual of Clinical Virology pp 41–42 New York: Raven Press;
    [Google Scholar]
  54. Wong G. H. W., Clark-Lewis L., McKimm-Breschkin J. L., Harris A. W., Schrader J. W. 1983; Interferon-γ induces enhanced expression of Ia and H-2 antigens on B lymphoid, macrophage, and myeloid cell lines. Journal of Immunology 131:788–793
    [Google Scholar]
  55. Yamashita Y., Shimokata K., Mizuno S., Yamaguchi H., Nishiyama Y. 1993; Down-regulation of the surface expression of class I MHC antigens by human cytomegalovirus. Virology 193:727–736
    [Google Scholar]
  56. York I. A., Roop C., Andrews D. W., Riddell S. R., Graham F. L., Johnson D. C. 1994; A cytosolic herpes simplex virus protein inhibits antigen presentation to CD8+ T lymphocytes. Cell 77:525–535
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-76-12-2987
Loading
/content/journal/jgv/10.1099/0022-1317-76-12-2987
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error