1887

Abstract

In this study, we characterized the B cell and T cell responses to the hydrophilic portion of hepatitis C virus (HCV) core protein in two strains of mice and identified the respective antigen determinants. BALB/c (H-2) and C57BL/6 (B6:H-2) mice were immunized by a subcutaneous injection of recombinant HCV core protein together with Freund’s complete adjuvant. The level of antibody production, as determined by ELISA, was consistently higher in BALB/c than in B6 mice. However, antibodies in sera from each strain bound to the N-terminal region of the core protein within amino acids 1 to 28 (MSTNPKPQRKIKRNTNRRPQDVKFPGGG), according to an experiment using non-overlapping peptides that covered the hydrophilic portion of HCV core protein. The T cell responses were also higher in BALB/c than in B6 mice with respect to the proliferative responses of the draining lymph node cells . By limiting dilution cultures of the draining lymph node cells repetitively stimulated with recombinant core protein, T cell clones were established from both strains of mice and characterized. The surface markers of these clones were Thy-1.2, CD3, TCRαβ, CD4 and CD8. The proliferative responses were inhibited in the presence of anti-CD4 or anti-MHC class II monoclonal antibodies. The T cell lines in BALB/c mice recognized an epitope in HCV core at amino acids 72 to 91 (EGRAWAQPGYPWPLYGNEGL). The T cell lines in B6 mice recognized an epitope at amino acids 55 to 74 (RPQPRGRRQPIPKARQPEGR). Thus, mice with different MHC haplotypes recognized different non-overlapping T cell antigenic determinants of HCV core proteins.

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1995-05-01
2024-03-29
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References

  1. Abe K., Inchauspe G., Shikata T., Prince A. M. 1992; Three different patterns of hepatitis C virus infection in chimpanzees. Hepatology 15:690–695
    [Google Scholar]
  2. Alter H. J., Purcell R., Shih J., Melpolder J., Houghton M., Choo Q. L., Kuo G. 1989; Detection of antibody to hepatitis C virus in prospectively followed transfusion recipients with acute and chronic non-A, non-B hepatitis. New England Journal of Medicine 321:1494–1500
    [Google Scholar]
  3. Alter M. J., Margolis H. S., Krawczybski K., Judson F., Mares A., Alexander W., Hu P. Y., Hu J., Miller J., Gerber A., Sampliner R. E. 1992; The natural history of community-acquired hepatitis C in the United States. New England Journal of Medicine 327:1899–1905
    [Google Scholar]
  4. Ando K., Moriyama T., Guidotti L., Wirth S., Schreiber R., Schlicht H. J., Huang S. N., Chisari F. 1993; Mechanisms of class I restricted immunopathology. A transgenic mouse model of fulminant hepatitis. Journal of Experimental Medicine 178:15410150–1554
    [Google Scholar]
  5. Bookman M. A., Swerdlow R., Matis L. A. 1987; Adoptive chemoimmunotherapy of murine leukemia with helper T lymphocyte clones. Journal of Immunology 139:3166–3170
    [Google Scholar]
  6. Bortolotti F., Tagger A., Cadrobbi P., Pregliasco F., Ribero M. L., Alberti A. 1991; Antibodies to hepatitis C virus in community-acquired acute non-A, non-B hepatitis. Journal of Hepatology 12:176–180
    [Google Scholar]
  7. Botarelli P., Brunetto M., Minutello M., Calvo P., Unutmaz D., Weiner A., Choo Q.-L., Shuster J., Kuo G., Bonino F., Houghton M., Abrignani S. 1993; T-lymphocyte response to hepatitis C virus in different clinical courses of infection. Gastroenterology 104:580–587
    [Google Scholar]
  8. Bukh J., Purcell R. H., Miller R. H. 1994; Sequence analysis of the core gene of the 14 hepatitis C virus genotypes. Proceedings of the National Academy of Sciences, USA 91:8239–8243
    [Google Scholar]
  9. Cha T.-A., Beall E., Irvine B., Kolberg J., Chien D., Kuo G., Urdea M. S. 1992; At least five related, but distinct, hepatitis C virus genotypes exist. Proceedings of the National Academy of Sciences, USA 89:7144–7148
    [Google Scholar]
  10. Chiba J., Ohba H., Matsuura Y., Watanabe Y., Katayama T., Kikuchi S., Saito I., Miyamura T. 1991; Serodiagnosis of hepatitis C virus (HCV) infection with an HCV core protein molecularly expressed by a recombinant baculovirus. Proceedings of the National Academy of Sciences, USA 88:4641–4645
    [Google Scholar]
  11. Ching W.-M., Wychowski C., Beach M., Wang H., Davies C., Carl M., Bradley D., Alter A. J., Feinstone S., Shih W.-K. 1992; Interaction of immune sera with synthetic peptides corresponding to the structural protein region of hepatitis C virus. Proceedings of the National Academy of Sciences, USA 89:3190–3194
    [Google Scholar]
  12. Choo Q. L., Kuo G., Weiner J., Overby L. R., Bradley D. W., Houghton M. 1989; Isolation of a cDNA clone derived from blood-borne non-A, non-B viral hepatitis genome. Science 244:359–362
    [Google Scholar]
  13. Choo Q.-L., Richman K. H., Han J. H., Berger K., Lee C., Dong D., Gallegos C., Coit D., Medina-Seiby A., Barr P. J., Weiner A. J., Bradley D. W., Kuo G., Houghton M. 1991; Genetic organization and diversity of the hepatitis C virus. Proceedings of the National Academy of Sciences, USA 88:2451–2455
    [Google Scholar]
  14. Choo Q.-L., Kuo G., Ralaston R., Weiner A., Chen D., Van Nest G., Han J., Berger K., Thudium K., Kuo C., Kansopon J., McFarland J., Tabrizi A., Ching K., Moss B., Cummins L. B., Houghton M., Muchmore E. 1994; Vaccination of chimpanzees against infection by the hepatitis C virus. Proceedings of the National Academy of Sciences, USA 91:1294–1298
    [Google Scholar]
  15. Colombo M., Kuo G., Choo Q.-L., Donato M. F., Del Ninno E., Tommasini M. A., Dioguardi N., Houghton M. 1989; Prevalence of antibodies to hepatitis C virus in Italian patients with hepatocellular carcinoma. Lancet ii:1006–1008
    [Google Scholar]
  16. Dienstag J. L. 1983; Non-A, non-B hepatitis: recognition, epidemiology, and clinical features. Gastroenterology 85:439–462
    [Google Scholar]
  17. Dienstag J. 1990; Hepatitis non-A, non-B: C at last. Gastroenterology 99:1177–1180
    [Google Scholar]
  18. Earl P. L., Moss B., Morrison R. P., Wehrly K., Nishio J., Chesebro B. 1986; T-lymphocyte priming and protection against Friend leukemia by vaccinia-retrovirus env gene recombinant. Science 234:728–731
    [Google Scholar]
  19. Farci P., Alter A. J., Wong D., Miller R. H., Shih J. W., Jett B., Purcell R. H. 1991; A long-term study of hepatitis C virus replication in non-A, non-B hepatitis. New England Journal of Medicine 325:98–104
    [Google Scholar]
  20. Ferrari C., Valli A., Galati L., Penna A., Scaccaglia P., Giuberti T., Schianchi C., Missale G., Martin M. G., Fiaccadori F. 1994; T-cell response to structural and nonstructural hepatitis C virus antigens in persistent and self-limited hepatitis C virus infections. Hepatology 19:286–295
    [Google Scholar]
  21. Fujiwara H., Fukuzawa M., Yoshioka T., Nakajima H., Hamaoka T. 1984; The role of tumor-specific Lyt-1+ 2 T cells in eradicating tumor cells in vivo. I. Lyt-1+ 2 T cells do not necessarily require recruitment of host′s cytotoxic T cell precursors for implementation of in vivo immunity. Journal of Immunology 133:1671–1676
    [Google Scholar]
  22. Greenberg P. D., Cheever M. A., Fefer A. 1981; Eradication of disseminated murine leukemia by chemoimmunotherapy with cyclophosphamide and adoptively transferred immune syngeneic Lyt-L+2 lymphocytes. Journal of Experimental Medicine 154:952–963
    [Google Scholar]
  23. Harada S., Watanabe Y., Suzuki T., Katayama T., Takebe Y., Saito I., Miyamura T. 1991; Expression of processed core protein of hepatitis C virus in mammalian cells. Journal of Virology 65:3015–3021
    [Google Scholar]
  24. Hosein B., Fang C., Popovsky M., Ye J., Zhang M., Wang C.-Y. 1991; Improved serodiagnosis of hepatitis C virus infection with synthetic peptide antigen from capsid protein. Proceedings of the National Academy of Sciences, USA 88:3647–3651
    [Google Scholar]
  25. Hosmalin A., Clirici M., Houghten R., Pendleton C. D., Flexner C., Lucey D. R., Moss B., Germain R. N., Shearer G. M., Berzofsky J. A. 1990; An Epitope in human immunodeficiency virus 1 reverse transcriptase recognized by both mouse and human cytotoxic T lymphocytes. Proceedings of the National Academy of Sciences, USA 87:2344–2348
    [Google Scholar]
  26. Houghton M., Weiner A., Han J., Kuo G., Choo Q.-L. 1991; Molecular biology of the hepatitis C viruses; implications for diagnosis, development and control of viral disease. Hepatology 14:381–388
    [Google Scholar]
  27. Ishida C., Matsumoto K., Fukuda K., Matsushita K., Shiraki H., Maeda Y. 1993; Detection of antibodies to hepatitis C virus (HCV) structural proteins in anti-HCV-positive sera by an enzyme-linked immunosorbent assay using synthetic peptides as antigens. Journal of Clinical Microbiology 31:936–940
    [Google Scholar]
  28. Iwashiro M., Kondo T., Shimizu T., Yamagishi H., Takahashi K., Matsubayashi Y., Masuda T., Otaka A., Fujii N., Ishimoto A., Miyazawa M., Robertson M. N., Chesebro B., Kuribayashi K. 1993; Multiplicity of virus-encoded helper T-cell epitopes expressed on FBL-3 tumor cells. Journal of Virology 67:4533–1542
    [Google Scholar]
  29. Jamielson B. D., Butler L. D., Ahmed R. 1987; Effective clearance of a persistent viral infection requires cooperation between virus-specific Lyt2+ T cells and nonspecific bone marrow-derived cells. Journal of Virology 61:3930–3937
    [Google Scholar]
  30. Kato N., Hijikata M., Ootsuyama 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-Β hepatitis. Proceedings of the National Academy of Sciences, USA 87:9524–9528
    [Google Scholar]
  31. Kato N., Sekiya H., Ootsuyama Y., Nakazawa T., Hijikata M., Ohkoshi S., Shimotohno K. 1993; Humoral immune response to hypervariable region 1 of the putative envelope glycoprotein (gp70) of hepatitis C virus. Journal of Virology 67:3923–3930
    [Google Scholar]
  32. Kita H., Moriyama T., Kaneko T., Harase I., Nomura M., Miura Η., 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]
  33. Kiyosawa K., Sodeyama T., Tanaka E., Gibo Y., Yoshizawa K., Nakano Y., Furuta S., Akahane Y., Nishioka K., Purcell R. H., Alter H. J. 1990; Interrelationship of blood transfusion, non-A, non-B hepatitis and hepatocellular carcinoma: analysis by detection of antibody to hepatitis C virus. Hepatology 12:671–675
    [Google Scholar]
  34. 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]
  35. Koziel M., Dudley D., Afdhal N., Choo Q.-L., Houghton M., Ralston R., Walker B. 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]
  36. Kuo G., Choo Q.-L., Alter H., Gitnick G., Redeker A., Purcel R., Miyamura T., Dienstag J., Alter M., Stevens C., Tegtmeier G., Bonino F., Colombo M., Lee W. S., Kuo G., Berger K., Shuster J., Overby L., Bradley D., Houghton M. 1989; An assay for circulating antibodies to a major etiologic form of human non-A, non-B hepatitis. Science 244:362–364
    [Google Scholar]
  37. Martell M., Esteban J. I., Quer J., Genesca J., Weiner A., Esteban R., Guardia J., Gomez J. 1992; Hepatitis C virus (HCV) circulates as a population of different but closely related genomes: quasispecies nature of HCV genome distribution. Journal of Virology 66:3225–3229
    [Google Scholar]
  38. Masaki T., Fujihashi T., Nakamura K., Soejima M. 1981; Studies on a new proteolytic enzyme from Achromobacter lyticus M497-1. II. Specificity and inhibition studies of Achromobacter protease. Biochimica et Biophysica Acta 660:51–55
    [Google Scholar]
  39. Matis L. A., Ruscetti S. K., Longo D. L., Jacobson S., Brown E. J., Zinn S., Kruisbeek A. M. 1985; Distinct proliferative T cell clonotypes are generated in response to a murine retrovirus-induced syngeneic T cell leukemia: viral gp70 antigen-specific MT4+ clones and Lyt-2+ cytolytic clones which recognize a tumor specific cell surface antigen. Journal of Immunology 135:703–713
    [Google Scholar]
  40. Milich D., McLachlan A., Moriarty A., Thornton G. B. 1987; Immune response to hepatitis B virus core antigen (HBcAg): localization of T cell recognition sites within HBcAg/HBeAg. Journal of Immunology 139:1223–1231
    [Google Scholar]
  41. Miller R. H., Purcell R. H. 1990; Hepatitis C virus shares amino acid sequence similarity with pestiviruses and flaviviruses as well as members of two plant virus supergroups. Proceedings of the National Academy of Sciences, USA 87:2057–2061
    [Google Scholar]
  42. Miyamura T., Saito I., Katayama T., Kikuchi S., Tateda A., Houghton M., Choo Q.-L., Kuo G. 1990; Detection of antibody against antigen expressed by molecularly cloned hepatitis C virus cDNA: application to diagnosis and blood screening for posttransfusion hepatitis. Proceedings of the National Academy of Sciences, USA 87:983–987
    [Google Scholar]
  43. Morioka A., Iwashiro M., Matubayashi Y., Teramura Y., Kuribayashi K. 1994; Effects of non-MHC background genes on the induction of CD4+T cells that prevent rejection of a highly immunogenic tumor, FBL-3. International Immunology 6:839–846
    [Google Scholar]
  44. Moriyama T., Guilhot S., Klopchin K., Moss B., Pinkert C., Palmiter R., Brinster R., Kanagawa O., Chisari F. 1990; Immunobiology and pathogenesis of hepatocellular injury in hepatitis B virus transgenic mice. Science 248:361–364
    [Google Scholar]
  45. Moskophidis D., Lechner F., Hengartner H., Zinkernagel R. 1994; MHC class I and non-MHC-linked capacity for generating an anti-viral CTL response determines susceptibility to CTL exhaustion and establishment of virus persistence in mice. Journal of Immunology 152:4976–4983
    [Google Scholar]
  46. Nasoff M. S., Zebedee S. L., Inchauspe G., Prince A. 1991; Identification of an immunodominant epitope within the capsid protein of hepatitis C virus. Proceedings of the National Academy of Sciences, USA 88:5462–5466
    [Google Scholar]
  47. Ogata N., Alter H. J., Miller R. H., Purcell R. H. 1991; Nucleotide sequence and mutation rate of the H strain of hepatitis C virus. Proceedings of the National Academy of Sciences, USA 88:3392–3396
    [Google Scholar]
  48. Okamoto H., Okada S., Sugiyama Y., Yotsumoto S., Tanaka T., Yoshizawa H., Tsuda F., Miyakawa Y., Mayumi M. 1990a; The 5′-terminal sequence of the hepatitis C virus genome. Japanese Journal of Experimental Medicine 60:167–177
    [Google Scholar]
  49. Okamoto H., Munekata E., Tsuda F., Takahashi K., Yotsumoto S., Tanaka T., Tachibana V., Akahane Y., Sugai Y., Miyakawa Y., Mayumi M. 1990b; Enzyme-linked immunosorbent assay for antibodies against the capsid protein of hepatitis C virus with a synthetic oligopeptide. Japanese Journal of Experimental Medicine 60:223–233
    [Google Scholar]
  50. Oldstone Μ. 1989; Viral persistence. Cell 56:517–520
    [Google Scholar]
  51. Perkins D. L., Lai M.-Z., Smith J. A., Gefter M. L. 1989; Identical peptides recognized by MHC class I and II restricted T cells. Journal of Experimental Medicine 170:279–289
    [Google Scholar]
  52. Peters M., Vierling J., Gershwin E., Milich D., Chisari F., Hoofnagle J. 1991; Immunology and liver. Hepatology 13:977–994
    [Google Scholar]
  53. Plata F., Langlade-Demoyen P., Abastado J. P., Berbar T., Kourilsky P. 1987; Retrovirus antigens recognized by cytolytic T lymphocytes activate tumor rejection in vivo. Cell 48:231–240
    [Google Scholar]
  54. Ralston R., Thudium K., Berger K., Kuo C., Gervase B., Hall J., Selby M., Kuo G., Houghton M., Choo Q.-L. 1993; Characterization of hepatitis C virus envelope glycoprotein complexes expressed by recombinant vaccinia viruses. Journal of Virology 67:6753–6761
    [Google Scholar]
  55. Saito I., Miyamura T., Ohbayashi A., Harada Η., Katayama T., Kikuchi S., Watanabe Y., Koi S., Onji Μ., Ohta Y., Choo Q.-L., Houghton M., Kuo G. 1990; Hepatitis C virus infection is associated with development of hepatocellular carcinoma. Proceedings of the National Academy of Sciences, USA 87:6547–6549
    [Google Scholar]
  56. Sällberg M., Ruden U., Wahren B., Magnius L. O. 1992; Immune response to a single peptide containing an immunodominant region of hepatitis C virus core protein; the iso types and the recognition site. Immunology Letters 33:27–33
    [Google Scholar]
  57. Seeff L. B., Buskell-Bales Z., Weight E. C., Durako S. J., Alter H. J., Iber F., Hollinger F., Gitnick G., Knodell R., Perillo R. 1992; Long term mortality after transfusion-associated non-A, non-B hepatitis. New England Journal of Medicine 327:1906–1911
    [Google Scholar]
  58. Seki M., Honda Y., Kondo J., Fukuda K., Ohta K., Sugimoto J., Yamada E. 1994; Effective production of hepatitis C virus core antigen having high purity in Escherichia coli. Journal of Biotechnology 38:229–241
    [Google Scholar]
  59. Shirai M., Akatsuka T., Pendleton C. D., Houghten R., Wychowski C., Mihalik K., Feinstone S., Berzofsky J. A. 1992; Induction of cytotoxic T cells to a cross-reactive epitope in the hepatitis C virus non-structural RNA polymerase-like protein. Journal of Virology 66:4098–4106
    [Google Scholar]
  60. Shirai M., Okada H., Nishioka M., Akatsuka T., Wychowski C., Houghten R., Pendlton C. D., Feinstone S. M., Berzofsky J. A. 1994; An epitope in hepatitis C virus core region recognized by cytotoxic T cells in mice and humans. Journal of Virology 68:3334–3342
    [Google Scholar]
  61. Takahashi K., Kitamura N., Shibui T., Kamizono M., Matsui R., Yoshiyama Y., Maeda T., Kondo J., Honda Y., Yamada E., Shimizu Y., Teranishi Y., Nakanishi S. 1990; Cloning, sequencing and expression in Escherichia coli of cDNA for a non-A, non-B hepatitis-associated microtubular aggregates protein. Journal of General Virology 71:2005–2011
    [Google Scholar]
  62. Takamizawa A., Mori C., Fuke I., Manabe S., Murakami S., Fujita J., Onishi E., Andoh T., Yoshida I., Okayama H. 1991; Structure and organization of the hepatitis C virus genome isolated from human carriers. Journal of Virology 65:1105–1113
    [Google Scholar]
  63. Takeuchi K., Kubo Y., Boonmar S., Watanabe Y., Katayama T., Choo Q.-L., Kuo G., Houghton M., Saito I., Miyamura T. 1990a; Nucleotide sequence of core and envelope genes of the hepatitis C virus genome derived directly from human healthy carriers. Nucleic Acids Research 18:4626
    [Google Scholar]
  64. Takeuchi K., Boonmar S., Kubo Y., Katayama T., Harada H., Ohbayashi A., Choo Q.-L., Kuo G., Houghton Μ., Saito I., Miyamura T. 1990b; Hepatitis C viral cDNA clones isolated from a healthy carrier donor implicated in post-transfusion non-A, non-B hepatitis. Gene 91:287–291
    [Google Scholar]
  65. Takeuchi K., Kubo Y., Boonmar S., Watanabe Y., Katayama T., Choo Q.-L., Kuo G., Houghton M., Saito I., Miyamura T. 1990c; The putative nucleocapsid and envelope protein genes of hepatitis C virus determined by comparison of the nucleotide sequences of two isolates derived from an experimentally infected chimpanzee and healthy human carriers. Journal of General Virology 71:3027–3033
    [Google Scholar]
  66. Udono Η., Mieno M., Shiku Η., Nakayama E. 1989; The roles of CD8+ and CD4+ cells in tumor rejection. Japanese Journal of Cancer Research 80:649–654
    [Google Scholar]
  67. Weiner A. J., Brauer M. J., Rosenblatt J., Richman K. H., Tung J., Bonino F., Saracco G., Choo Q.-L., Houghton M., Han J. H. 1991; Variable and hypervariable domains are found in the regions of HCV corresponding to the flavivirus envelope and NS1 proteins and the pestivirus envelope glycoproteins. Virology 180:842–848
    [Google Scholar]
  68. Yap K. L., Ada G. L., McKenzie I. F. C. 1978; Transfer of specific cytotoxic T lymphocytes protects mice inoculated with influenza virus. Nature 273:238–239
    [Google Scholar]
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