1887

Journal of General Virology header logo

Volume 83, Issue 3

Presentation of a new H-2D-restricted epitope in the Tax protein of human T-lymphotropic virus type I is enhanced by the proteasome inhibitor lactacystin Free

Abstract

Tax, the -activator of human T-lymphotropic virus type I (HTLV-I), is the dominant target antigen for cytotoxic T lymphocytes (CTLs) in the majority of infected individuals, although the reason for this immunodominance is not clear. Tax has been shown to associate physically with the proteasome, a protease that is responsible for the generation of the majority of major histocompatibility complex (MHC) class I ligands recognized by CTLs. This association could lead to the preferential targeting of Tax to the MHC class I pathway and account for its high immunogenicity. Here, the CTL response to Tax was investigated in mice by priming with a Tax expression vector and boosting with a Tax recombinant vaccinia virus (modified vaccinia virus Ankara strain). This approach led to the identification of a new H-2D-restricted epitope in Tax, amino acid residues 38–46, sequence ARLHRHALL. Surprisingly, presentation of this epitope was found to be enhanced by the proteasome inhibitor lactacystin, although Tax was shown to associate with proteasomes in murine cells. The difficulties encountered in generating Tax-specific CTL responses and the results of enzyme-linked immunospot (ELISpot) analysis suggested that Tax is only poorly immunogenic for CTLs in mice. Therefore, the immunodominance of Tax in human CTL responses to HTLV-I is probably not due to an intrinsic property of the protein itself, such as an association with the proteasome, but instead may result from the fact that Tax is the predominant protein synthesized early after infection.

  • Received:
  • Accepted:
  • Published Online:
© Microbiology Society
Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-83-3-641
2002-03-01
2024-04-25
Loading full text...

Full text loading...

/deliver/fulltext/jgv/83/3/0830641a.html?itemId=/content/journal/jgv/10.1099/0022-1317-83-3-641&mimeType=html&fmt=ahah

References

  1. Anton L. C., Snyder H. L., Bennink J. R., Vinitsky A., Orlowski M., Porgador A., Yewdell J. W. 1998; Dissociation of proteasomal degradation of biosynthesized viral proteins from generation of MHC class I-associated antigenic peptides. Journal of Immunology 160:4859–4868
     [Google Scholar]
  2. Apostolopoulos V., Haurum J. S., McKenzie I. F. 1997; MUC1 peptide epitopes associated with five different H-2 class I molecules. European Journal of Immunology 27:2579–2587
     [Google Scholar]
  3. Bangham C. R. M. 2000; HTLV-I infections. Journal of Clinical Pathology 53:581–586
     [Google Scholar]
  4. Bangham C. R. M., Kermode A. G., Hall S. E., Daenke S. 1996; The cytotoxic T-lymphocyte response to HTLV-I: the main determinant of disease?. Seminars in Virology 7:41–48
     [Google Scholar]
  5. Bangham C. R. M., Hall S. E., Jeffery K. J. M., Vine A. M., Witkover A., Nowak M. A., Wodarz D., Usuku K., Osame M. 1999; Genetic control and dynamics of the cellular immune response to the human T-leukaemia virus, HTLV-I. Philosophical Transactions of the Royal Society of London B Biological Sciences 354:691–700
     [Google Scholar]
  6. Beraud C., Greene W. C. 1996; Interaction of HTLV-I Tax with the human proteasome: implications for NF-κB induction. Journal of Acquired Immune Deficiency Syndrome and Human Retrovirology 13:76–84
     [Google Scholar]
  7. Berezutskaya E., Bagchi S. 1997; The human papillomavirus E7 oncoprotein functionally interacts with the S4 subunit of the 26 S proteasome. Journal of Biological Chemistry 272:30135–30140
     [Google Scholar]
  8. Cann A. J., Chen I. S. Y. 1996; Human T-cell leukaemia virus types I and II. In Fields Virology pp 1849–1880 Edited by Fields B. N., Knipe D. M., Howley P. M. Philadelphia: Lippincott–Raven;
     [Google Scholar]
  9. Cerundolo V., Benham A., Braud V., Mukherjee S., Gould K., Macino B., Neefjes J., Townsend A. 1997; The proteasome-specific inhibitor lactacystin blocks presentation of cytotoxic T lymphocyte epitopes in human and murine cells. European Journal of Immunology 27:336–341
     [Google Scholar]
  10. Chakrabarti S., Brechling K., Moss B. 1985; Vaccinia virus expression vector: coexpression of β-galactosidase provides visual screening of recombinant virus plaques. Molecular and Cellular Biology 5:3403–3409
     [Google Scholar]
  11. Ciminale V., Pavlakis G. N., Derse D., Cunningham C. P., Felber B. K. 1992; Complex splicing in the human T-cell leukemia virus (HTLV) family of retroviruses: novel mRNAs and proteins produced by HTLV type I. Journal of Virology 66:1737–1745
     [Google Scholar]
  12. de Bergeyck V., De Plaen E., Chomez P., Boon T., Van Pel A. 1994; An intracisternal A-particle sequence codes for an antigen recognised by syngeneic cytolytic T lymphocytes on a mouse spontaneous leukemia. European Journal of Immunology 24:2203–2212
     [Google Scholar]
  13. Dethlefs S., Escriou N., Brahic M., van den Werf S., Larsson-Sciard E.-L. 1997; Theiler’s virus and Mengo virus induce cross-reactive cytotoxic T lymphocytes restricted to the same immunodominant VP2 epitope in C57BL/6 mice. Journal of Virology 71:5361–5365
     [Google Scholar]
  14. Dick L. R., Cruikshank A. A., Grenier L., Melandri F. D., Nunes S. L., Stein R. L. 1996; Mechanistic studies on the inactivation of the proteasome by lactacystin: a central role for clasto-lactacystin β-lactone. Journal of Biological Chemistry 271:7273–7276
     [Google Scholar]
  15. Elliott J. F., Albrecht G. R., Gilladoga A., Handunnetti S. M., Neequaye J., Lallinger G., Minjas J. N., Howard R. J. 1990; Genes for Plasmodium falciparum surface antigens cloned by expression in COS cells. Proceedings of the National Academy of Sciences, USA 87:6363–6367
     [Google Scholar]
  16. Fenteany G., Standaert R. F., Lane W. S., Choi S., Corey E. J., Schreiber S. L. 1995; Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin. Science 268:726–731
     [Google Scholar]
  17. Gould K. G., Scotney H., Brownlee G. G. 1991; Characterization of two distinct major histocompatibility complex class I Kk-restricted T-cell epitopes within the influenza A/PR/8/34 virus hemagglutinin. Journal of Virology 65:5401–5409
     [Google Scholar]
  18. Groll M., Ditzel L., Löwe J., Stock D., Bochtler M., Bartunik H. D., Huber R. 1997; Structure of 20S proteasome from yeast at 2·4 Å resolution. Nature 386:463–471
     [Google Scholar]
  19. Hanke T., Blanchard T. J., Schneider J., Hannan C. M., Becker M., Gilbert S. C., Hill A. V. S., Smith G. L., McMichael A. 1998; Enhancement of MHC class I-restricted peptide-specific T cell induction by a DNA prime/MVA boost vaccination regime. Vaccine 16:439–445
     [Google Scholar]
  20. Hanon E., Hall S., Taylor G. P., Saito M., Davis R., Tanaka Y., Usuku K., Osame M., Weber J. N., Bangham C. R. M. 2000; Abundant Tax protein expression in CD4+ T cells infected with human T-cell lymphotropic virus type I (HTLV-I) is prevented by cytotoxic T lymphocytes. Blood 95:1386–1392
     [Google Scholar]
  21. Hidaka M., Inoue J., Yoshida M., Seiki M. 1988; Post-transcriptional regulator (rex) of HTLV-1 initiates expression of viral structural proteins but suppresses expression of regulatory proteins. EMBO Journal 7:519–523
     [Google Scholar]
  22. Huang J., Kwong J., Sun E. C.-Y., Liang T. J. 1996; Proteasome complex as a potential cellular target of hepatitis B virus X protein. Journal of Virology 70:5582–5591
     [Google Scholar]
  23. Jacobson S., Shida H., McFarlin D. E., Fauci A. S., Koenig S. 1990; Circulating CD8+ cytotoxic T lymphocytes specific for HTLV-I pX in patients with HTLV-I associated neurological disease. Nature 348:245–248
     [Google Scholar]
  24. Kannagi M., Sugamura K., Kinoshita K.-I., Uchino H., Hinuma Y. 1984; Specific cytolysis of fresh tumor cells by an autologous killer T cell line derived from an adult T cell leukemia/lymphoma patient. Journal of Immunology 133:1037–1041
     [Google Scholar]
  25. Kannagi M., Harada S., Maruyama I., Inoko H., Igarashi H., Kuwashima G., Sato S., Morita M., Kidokoro M., Sugimoto M. and others 1991; Predominant recognition of human T cell leukaemia virus type I (HTLV-I) pX gene products by human CD8+ cytotoxic T cells directed against HTLV-I-infected cells. International Immunology 3:761–767
     [Google Scholar]
  26. Lee D. H., Goldberg A. L. 1998; Proteasome inhibitors: valuable new tools for cell biologists. Trends in Cell Biology 8:397–403
     [Google Scholar]
  27. Luckey C. J., King G. M., Marto J. A., Venketeswaran S., Maier B. F., Crotzer V. L., Colella T. A., Shabanowitz T. A. C. J., Hunt D. F., Engelhard V. H. 1998; Proteasomes can either generate or destroy MHC class I epitopes: evidence for nonproteasomal epitope generation in the cytosol. Journal of Immunology 161:112–121
     [Google Scholar]
  28. Lukacher A. E., Wilson C. S. 1998; Resistance to polyoma virus-induced tumors correlates with CTL recognition of an immunodominant H-2Dk-restricted epitope in the middle T protein. Journal of Immunology 160:1724–1734
     [Google Scholar]
  29. Mata M., Travers P. J., Liu Q., Frankel F. R., Paterson Y. 1998; The MHC class I-restricted immune response to HIV-gag in BALB/C mice selects a single epitope that does not have a predictable MHC-binding motif and binds to Kd through interactions between a glutamine at P3 and pocket D. Journal of Immunology 161:2985–2993
     [Google Scholar]
  30. Palombella V. J., Rando O. J., Goldberg A. L., Maniatis T. 1994; The ubiquitin-proteasome pathway is required for processing the NF-κB1 precursor protein and the activation of NF-κB. Cell 78:773–785
     [Google Scholar]
  31. Parker C. E., Daenke S., Nightingale S., Bangham C. R. M. 1992; Activated, HTLV-1-specific cytotoxic T-lymphocytes are found in healthy seropositives as well as in patients with tropical spastic paraparesis. Virology 188:628–636
     [Google Scholar]
  32. Parker C. E., Nightingale S., Taylor G. P., Weber J., Bangham C. R. M. 1994; Circulating anti-Tax cytotoxic T lymphocytes from human T-cell leukemia virus type I-infected people, with and without tropical spastic paraparesis, recognize multiple epitopes simultaneously. Journal of Virology 68:2860–2868
     [Google Scholar]
  33. Power C. A., Grand C. L., Ismail N., Peters N. C., Yurkowski D. P., Bretscher P. A. 1999; A valid ELISPOT assay for enumeration of ex vivo , antigen-specific, IFNγ-producing T cells. Journal of Immunological Methods 227:99–107
     [Google Scholar]
  34. Rammensee H.-G., Bachmann J., Emmerich N. P. N., Bachor O. A., Stevanivic S. 1999; SYFPEITHI: database for MHC ligands and peptide motifs. Immunogenetics 50:213–219
     [Google Scholar]
  35. Rock K. L., Gramm C., Rothstein L., Clark K., Stein R., Dick L., Hwang D., Goldberg A. L. 1994; Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented by MHC class I molecules. Cell 78:761–771
     [Google Scholar]
  36. Rossi F., Evstafieva A., Pedrali-Noy G., Gallina A., Milanesi G. 1997; HsN3 proteasomal subunit as a target for Human Immunodeficiency Virus type 1 Nef protein. Virology 237:33–45
     [Google Scholar]
  37. Rousset R., Desbois C., Bantignies F., Jalinot P. 1996; Effects on NF-κB1/p105 processing of the interaction between the HTLV-1 transactivator Tax and the proteasome. Nature 381:328–331
     [Google Scholar]
  38. Schneider J., Gilbert S. C., Blanchard T. J., Hanke T., Robson K. J., Hannan C. M., Becker M., Sinden R., Smith G. L., Hill A. V. S. 1998; Enhanced immunogenicity for CD8+ T cell induction and complete protective efficacy of malaria DNA vaccination by boosting with modified vaccinia virus Ankara. Nature Medicine 4:397–402
     [Google Scholar]
  39. Schwarz K., de Giuli R., Schmidtke G., Kostka S., van den Broek M., Kim K. B., Crews C. M., Kraft R., Groettrup M. 2000; The selective proteasome inhibitors lactacystin and epoxomicin can be used to either up- or down-regulate antigen presentation at nontoxic doses. Journal of Immunology 164:6147–6157
     [Google Scholar]
  40. Seeger M., Ferrell K., Frank R., Dubiel W. 1997; HIV-1 Tat inhibits the 20 S proteasome and its 11 S regulator-mediated activation. Journal of Biological Chemistry 272:8145–8148
     [Google Scholar]
  41. Tanaka Y., Isobe A., Masuda M., Tozawa H., Koyanagi Y., Yamamoto N., Shida H. 1991; Immunogenicity of human T cell leukemia virus type-I (HTLV-I) antigens for cytotoxic lymphocytes in the rat system. Journal of Immunology 147:3646–3652
     [Google Scholar]
  42. Tourdot S., Herath S., Gould K. G. 2001; Characterization of a new H-2Dk-restricted epitope prominent in primary influenza A virus infection. Journal of General Virology 82:1749–1755
     [Google Scholar]
  43. Townsend A. R. M., Gotch F. M., Davey J. 1985; Cytotoxic T lymphocytes recognize fragments of the influenza nucleoprotein. Cell 42:457–467
     [Google Scholar]
  44. Turnell A. S., Grand R. J. A., Gorbea C., Zhang X., Wang W., Mymryk J. S., Gallimore P. H. 2000; Regulation of the 26S proteasome by adenovirus E1A. EMBO Journal 19:4759–4773
     [Google Scholar]
  45. Uchiyama T. 1997; Human T cell leukaemia virus type I (HTLV-I) and human diseases. Annual Review of Immunology 15:15–37
     [Google Scholar]
  46. Vinitsky A., Anton L. C., Snyder H. L., Orlowski M., Bennink J. R., Yewdell J. W. 1997; The generation of MHC class I-associated peptides is only partially inhibited by proteasome inhibitors: involvement of nonproteasomal cytosolic proteases in antigen processing?. Journal of Immunology 159:554–564
     [Google Scholar]
  47. Wilson C. S., Moser J. M., Altman J. D., Jensen P. E., Lukacher A. E. 1999; Cross-recognition of two middle T protein epitopes by immunodominant polyoma virus-specific CTL. Journal of Immunology 162:3933–3941
     [Google Scholar]
  48. Yewdell J. W., Bennink J. R. 1999; Immunodominance in major histocompatibility complex class I-restricted T lymphocyte responses. Annual Review of Immunology 17:51–88
     [Google Scholar]
  49. Zhang Z., Torii N., Furusaka A., Malayaman N., Hu Z., Liang T. J. 2000; Structural and functional characterization of interaction between Hepatitis B virus X protein and the proteasome complex. Journal of Biological Chemistry 275:15157–15165
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-83-3-641
Loading
Presentation of a new H-2Dk-restricted epitope in the Tax protein of human T-lymphotropic virus type I is enhanced by the proteasome inhibitor lactacystin
J. Gen. Virol. 83, 641 (2002); https://doi.org/10.1099/0022-1317-83-3-641
/content/journal/jgv/10.1099/0022-1317-83-3-641
/content/journal/jgv/10.1099/0022-1317-83-3-641
Loading

Data & Media loading...

Most cited Most Cited RSS feed

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