1887

Abstract

In order to clarify the role of cytotoxic T lymphocytes (CTL) in hepatitis C virus (HCV) infection, an HLA- B35-restricted cytotoxic T cell epitope of HCV was identified using a strategy called reverse immuno- genetics. Twenty-eight of 53 HCV peptides carrying two anchor residues were selected as HLA-B*3501 binding peptides. These peptides were used to induce the specific cytotoxic T cells in peripheral blood lymphocytes from a patient with acute hepatitis C. Six HLA-B*3501 binding peptides induced the peptide-specific CTL. One (HPNIEEVAL) of five peptides was confirmed as the epitope by the specific T cell clones. A sequence identical to the epitope was detected in isolates of the virus from the patient and a strong CTL response to this epitope was observed in the acute phase of hepatitis C but not in the recovery phase. The specific CTL for this epitope were not detected in peripheral blood lymphocytes from patients with chronic hepatitis C. Together these results suggest that the CTL specific for this epitope have an important role in the elimination of the virus in the patient.

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1998-07-01
2024-12-07
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References

  1. Alter M. J., Margolis H. S., Krawczynski K., Judson F. N., Mares A., Alexander W. J., Hu P. Y., Miller J. K., Gerber M. A., Sampliner R. E., Meeks E. L., Beach M. J. 1992; The natural history of community- acquired hepatitis C in the United States. New England Journal of Medicine 327:1899–1905
    [Google Scholar]
  2. Barnaba V., Franco A., Alberti A., Balsano C., Benvenuto R., Balsano F. 1989; Recognition of hepatitis B virus envelope proteins by liver-infiltrating lymphocytes in chronic HBV infection. Journal of Immunology 143:2650–2655
    [Google Scholar]
  3. Battegay M., Fikes J., Di Bisceglie A. M., Wentworth P. A., Sette A., Celis E., Ching W. M., Grakoui A., Rice C. M., Kurokohchi K., Berzofsky J. A., Hoofnagle J. H., Feinstone S. M., Akatsuka T. 1995; Patients with chronic hepatitis C have circulating cytotoxic T cells which recognize hepatitis C virus-encoded peptides binding to HLA-A2.1 molecules. Journal of Virology 69:2462–2470
    [Google Scholar]
  4. Borrow P., Lewicki H., Wei X., Horwitz M. S., Peffer N., Heyers H., Nelson J., Gairin J. E., Hahn B. H., Oldstone M. B. A., Shaw G. M. 1997; Antiviral pressure exerted by HIV-1-specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus. Nature Medicine 3:205–211
    [Google Scholar]
  5. Cerny A., McHutchison J. G., Pasquinelli C., Brown M. E., Brothers M. A., Grabscheid B., Fowler P., Houghton M., Chisari F. V. 1995; Cytotoxic T lymphocyte response to hepatitis C virus-derived peptides containing the HLA A2.1 binding motif. Journal of Clinical Investigation 95:521–530
    [Google Scholar]
  6. Dienstag J. L. 1997; Sexual and prenatal transmission of hepatitis C. Hepatology 26: suppl 6670
    [Google Scholar]
  7. Eisenlohr L. C., Yewdell J. W., Bennik J. R. 1992; Flanking sequences influence the presentation of an endogenously synthesized peptide to cytotoxic T lymphocytes. Journal of Experimental Medicine 175:481–487
    [Google Scholar]
  8. Engelhard V. H. 1994; Structure of peptides associated with MHC class I molecules. Current Opinion in Immunology 6:13–23
    [Google Scholar]
  9. Erickson A. L., Houghton M., Choo Q. L., Weiner A. J., Ralston R., Muchmore E., Walker C. M. 1993; Hepatitis C virus-specific CTL responses in the liver of chimpanzees with acute and chronic hepatitis C. Journal of Immunology 151:4189–4199
    [Google Scholar]
  10. Falk K., Rötzschke O., Stevanovíc S., Jung G., Rammensee H. G. 1991; Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature 351:290–296
    [Google Scholar]
  11. Falk K., Rötzschke O., Grahovac B., Schendel D., Stevanovíc S., Jung G., Rammensee H. G. 1993; Peptide motifs of HLA-B35 and -B37 molecules. Immunogenetics 38:161–162
    [Google Scholar]
  12. Falk K., Rötzschke O., Grahovac B., Schendel D., Stevanovíc S., Jung G., Rammensee H. G. 1994; Erratum: Peptide motifs of HLA- B35 and -B37 molecules. Immunogenetics 39:379
    [Google Scholar]
  13. Hill A. V. S., Elvin J., Willis A. C., Aidoo M., Allsopp C. E. M., Gotch F. M., Gao X. M., Takiguchi M., Greenwood B. M., Townsend A. R. M., McMichael A. J., Whittle H. C. 1992; Molecular analysis of the association of HLA-B53 and resistance to severe malaria. Nature 360:434–439
    [Google Scholar]
  14. Ikeda-Moore Y., Tomiyama H., Miwa K., Oka S., Iwamoto A., Kaneko Y., Takiguchi M. 1997; Identification and characterization of multiple HLA-A24-restricted HIV-1 CTL epitopes: strong epitopes are derived from V region of HIV-1. Journal of Immunology 159:6242–6252
    [Google Scholar]
  15. Inoue Y., Miyamura T., Unayama T., Takahashi K., Saito I. 1991; Maternal transfer of HCV. Nature 353:609
    [Google Scholar]
  16. Jardetzky T. S., Lane W. S., Robinson R. A., Madden D. R., Wiley D. C. 1991; Identification of self peptides bound to purified HLA-B27. Nature 353:326–329
    [Google Scholar]
  17. Kaneko T., Nakamura I., Kita H., Hiroishi K., Moriyama T., Imawari M. 1996; Three new cytotoxic T cell epitopes identified within the hepatitis C virus nucleoprotein. Journal of General Virology 77:1305–1309
    [Google Scholar]
  18. Kato N., Hijikata M., Oosuyama Y., Nakagawa M., Ohkoshi S., Sugimura T., Shimotohno K. 1990; Molecular cloning of the human hepatitis C virus genome from Japanese patients with non-A, non-B hepatitis. Proceedings of the National Academy of Sciences, USA 87:9524–9528
    [Google Scholar]
  19. Kita H., Moriyama T., Kaneko T., Harase I., Nomura M., Miura H., Nakamura I., Yazaki Y., Imawari M. 1993; HLA B44-restricted cytotoxic T lymphocytes recognizing an epitope on hepatitis C virus nucleocapsid protein. Hepatology 18:1039–1044
    [Google Scholar]
  20. Koziel M. J., Dudley D., Wong J. T., Dienstag J., Houghton M., Ralston R., Walker B. D. 1992; Intrahepatic cytotoxic T lymphocytes specific for hepatitis C virus in persons with chronic hepatitis. Journal of Immunology 149:3339–3344
    [Google Scholar]
  21. Koziel M. J., Dudley D., Afdhal N., Choo Q. L., Houghton M., Ralston R., Walker B. D. 1993; Hepatitis C virus (HCV)-specific cytotoxic T lymphocytes recognize epitopes in the core and envelope proteins of HCV. Journal of Virology 67:7522–7532
    [Google Scholar]
  22. Koziel M. J., Dudley D., Afdhal N., Grakoui A., Rice C. M., Choo Q. L., Houghton M., Walker B. D. 1995; HLA class I-restricted cytotoxic T lymphocytes specific for hepatitis C virus. Identification of multiple epitopes and characterization of patterns of cytokine release. Journal of Clinical Investigation 96:2311–2321
    [Google Scholar]
  23. Lukacher A. E., Braciale V. L., Braciale T. J. 1984; In vivo effector function of influenza virus-specific cytotoxic T lymphocyte clones is highly specific. Journal of Experimental Medicine 160:814–826
    [Google Scholar]
  24. Nayersina R., Fowler P., Guilhot S., Missale G., Cerny A., Schlicht H.-J., Vitiello A., Chesnut R., Person J. L., Redeker A. G., Chisari F. V. 1993; HLA A2 restricted cytotoxic T lymphocyte responses to multiple hepatitis B surface antigen epitopes during hepatitis B virus infection. Journal of Immunology 150:4659–4671
    [Google Scholar]
  25. Pamer E. G., Harty J. T., Bevan M. J. 1991; Precise prediction of a dominant class I MHC-restricted epitope of Listeria monocytogenes. Nature 353:852–855
    [Google Scholar]
  26. Penna A., Chisari F. V., Bertoletti A., Missale G., Fowler P., Giuberti T., Fiaccadori F., Ferrari C. 1991; Cytotoxic T lymphocytes recognize an HLA-A2-restricted epitope within the hepatitis B virus nucleocapsid antigen. Journal of Experimental Medicine 174:1565–1570
    [Google Scholar]
  27. Radka S. F., Kostyu D. D., Amos D. B. 1982; A monoclonal antibody directed against HLA-Bw6 epitope. Journal ofImmunology 128:2804–2806
    [Google Scholar]
  28. Rehermann B., Chang K.-M., McHutchison J. G., Kokka R., Houghton M., Chisari F. V. 1996; Quantitative analysis of the peripheral blood cytotoxic T lymphocyte response in patients with chronic hepatitis C virus infection. Journal of Clinical Investigation 98:1432–1440
    [Google Scholar]
  29. Rehermann B., Chang K.-M., McHutchison J. C., Kokka R., Houghton M., Rice C. M., Chisari F. V. 1996; Differential cytotoxic T- lymphocyte responsiveness to the hepatitis B and C viruses in chronically infected patients. Journal of Virology 70:7092–7102
    [Google Scholar]
  30. Riddell S. R., Watanbe K. S., Goodrich J. M., Li C. R., Agha M. E., Greenberg P. D. 1992; Restoration of viral immunity in immuno- deficient humans by the adoptive transfer of T cell clones. Science 257:238–240
    [Google Scholar]
  31. Schönbach C., Ibe M., Shiga H., Takamiya Y., Miwa K., Nokihara K., Takiguchi M. 1995; The tuning of peptide binding to HLA-B*3501 molecules by nonanchor residues. Journal of Immunology 154:5951–5958
    [Google Scholar]
  32. Schönbach C., Miwa K., Ibe M., Shiga H., Nokihara K., Takiguchi M. 1996; Refined peptide-HLA-B*3501 binding motif reveals differences in 9-mer to 11-mer peptide binding. Immunogenetics 45:121–129
    [Google Scholar]
  33. Seeff L. B. 1997; Natural history of hepatitis C. Hepatology 26: suppl 21–28
    [Google Scholar]
  34. Shiga H., Shioda T., Tomiyama H., Takamiya Y., Oka S., Kimura S., Yamaguchi Y., Gojoubori T., Rammensee H. G., Miwa K., Takiguchi M. 1996; Identification of multiple HIV-1 cytotoxic T-cell epitopes presented by human leukocyte antigen B35 molecules. AIDS 10:1075–1083
    [Google Scholar]
  35. Takamiya Y., Schönbach C., Nokihara K., Yamaguchi M., Ferrone S., Kano K., Egawa K., Takiguchi M. 1994; HLA-B*3501-peptide interactions : role of anchor residues of peptides in their binding to HLA- B*3501 molecules. International Immunology 6:255–261
    [Google Scholar]
  36. Takiguchi M., Kawaguchi G., Sekimata M., Hiraiwa M., Kariyone A., Takamiya Y. 1994; The role of conserved residue in pocket A and polymorphic residue in pocket E of HLA-B*3501 in presentation of human minor histocompatibility peptides to T cells. International Immunology 6:1345–1352
    [Google Scholar]
  37. Tanaka T., Kato N., Nakagawa N., Ootsuyama Y., Cho M. J., Nakazawa T., Hijikata M., Ishimura Y., Shimotohno K. 1992; Molecular cloning of hepatitis C virus genome from a single Japanese carrier: sequence variation within the same individual and among infected individuals. Virus Research 23:39–53
    [Google Scholar]
  38. Townsend A. M. R., Rothbard J., Gotch F. M., Bahadur G., Wraith D., McMichael A. J. 1986; The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell 44:959–968
    [Google Scholar]
  39. Wong D. K., Dudley D., Afdhal N., Rice C., Houghton M., Walker B. D., Koziel M. J. 1996; Liver-derived cytotoxic T lymphocytes in non-resolving hepatitis C infection (Abstract A1361). Digestive Diseases Week; San Francisco, CA, USA:
    [Google Scholar]
  40. Yamamoto J., Kariyone A., Akiyama N., Kano K., Takiguchi M. 1990; Presentation of human minor histocompatibility antigens by HLA-B35 or HLA-B38 molecules. Proceedings of the National Academy of Sciences, USA 87:2583–2587
    [Google Scholar]
  41. Yap K. L., Ada G. L., McKenzie I. F. C. 1978; Transfer of specific cytotoxic T lymphocytes protects mice incubated with influenza. Nature 273:238–239
    [Google Scholar]
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