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. 1995 Apr;69(4):2654–2658. doi: 10.1128/jvi.69.4.2654-2658.1995

Antiviral protective immunity induced by major histocompatibility complex class I molecule-restricted viral T-lymphocyte epitopes inserted in various positions in immunologically self and nonself proteins.

G Weidt 1, W Deppert 1, S Buchhop 1, H Dralle 1, F Lehmann-Grube 1
PMCID: PMC188949  PMID: 7533861

Abstract

Injection into mice of chimeric proteins consisting of a portion of either the simian virus 40 large tumor antigen or nonstructural protein 1 of influenza A virus or of the murine tumor suppressor p53 on one hand and T-cell epitopes of lymphocytic choriomeningitis virus on the other resulted in antiviral protective immunity, which was independent of the epitopes' position in the protein and the same whether the latter was immunologically nonself or self. Mice of different haplotypes were protected when the corresponding class I molecule-restricted epitopes had been inserted close to each other in one carrier protein.

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Selected References

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  1. Bachmann M. F., Kündig T. M., Freer G., Li Y., Kang C. Y., Bishop D. H., Hengartner H., Zinkernagel R. M. Induction of protective cytotoxic T cells with viral proteins. Eur J Immunol. 1994 Sep;24(9):2228–2236. doi: 10.1002/eji.1830240944. [DOI] [PubMed] [Google Scholar]
  2. Bergmann C. C., Tong L., Cua R., Sensintaffar J., Stohlman S. Differential effects of flanking residues on presentation of epitopes from chimeric peptides. J Virol. 1994 Aug;68(8):5306–5310. doi: 10.1128/jvi.68.8.5306-5310.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bergmann C., Stohlmann S. A., McMillan M. An endogenously synthesized decamer peptide efficiently primes cytotoxic T cells specific for the HIV-1 envelope glycoprotein. Eur J Immunol. 1993 Nov;23(11):2777–2781. doi: 10.1002/eji.1830231109. [DOI] [PubMed] [Google Scholar]
  4. Berthold H., Scanarini M., Abney C. C., Frorath B., Northemann W. Purification of recombinant antigenic epitopes of the human 68-kDa (U1) ribonucleoprotein antigen using the expression system pH6EX3 followed by metal chelating affinity chromatography. Protein Expr Purif. 1992 Feb;3(1):50–56. doi: 10.1016/1046-5928(92)90055-2. [DOI] [PubMed] [Google Scholar]
  5. Bonneau R. H., Fu T. M., Tevethia S. S. In vivo priming and activation of memory cytotoxic T-lymphocytes (CTL) by a chimeric simian virus 40 T antigen expressing an eight amino acid residue herpes simplex virus gB CTL epitope. Virology. 1993 Dec;197(2):782–787. doi: 10.1006/viro.1993.1657. [DOI] [PubMed] [Google Scholar]
  6. Brown M., McCormack M., Zinn K. G., Farrell M. P., Bikel I., Livingston D. M. A recombinant murine retrovirus for simian virus 40 large T cDNA transforms mouse fibroblasts to anchorage-independent growth. J Virol. 1986 Oct;60(1):290–293. doi: 10.1128/jvi.60.1.290-293.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chimini G., Pala P., Sire J., Jordan B. R., Maryanski J. L. Recognition of oligonucleotide-encoded T cell epitopes introduced into a gene unrelated to the original antigen. J Exp Med. 1989 Jan 1;169(1):297–302. doi: 10.1084/jem.169.1.297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Deckhut A. M., Lippolis J. D., Tevethia S. S. Comparative analysis of core amino acid residues of H-2D(b)-restricted cytotoxic T-lymphocyte recognition epitopes in simian virus 40 T antigen. J Virol. 1992 Jan;66(1):440–447. doi: 10.1128/jvi.66.1.440-447.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Del Val M., Schlicht H. J., Ruppert T., Reddehase M. J., Koszinowski U. H. Efficient processing of an antigenic sequence for presentation by MHC class I molecules depends on its neighboring residues in the protein. Cell. 1991 Sep 20;66(6):1145–1153. doi: 10.1016/0092-8674(91)90037-y. [DOI] [PubMed] [Google Scholar]
  10. Del Val M., Schlicht H. J., Volkmer H., Messerle M., Reddehase M. J., Koszinowski U. H. Protection against lethal cytomegalovirus infection by a recombinant vaccine containing a single nonameric T-cell epitope. J Virol. 1991 Jul;65(7):3641–3646. doi: 10.1128/jvi.65.7.3641-3646.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Eisenlohr L. C., Yewdell J. W., Bennink J. R. Flanking sequences influence the presentation of an endogenously synthesized peptide to cytotoxic T lymphocytes. J Exp Med. 1992 Feb 1;175(2):481–487. doi: 10.1084/jem.175.2.481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Engelhard V. H. Structure of peptides associated with class I and class II MHC molecules. Annu Rev Immunol. 1994;12:181–207. doi: 10.1146/annurev.iy.12.040194.001145. [DOI] [PubMed] [Google Scholar]
  13. Fu T. M., Bonneau R. H., Tevethia M. J., Tevethia S. S. Simian virus 40 T antigen as a carrier for the expression of cytotoxic T-lymphocyte recognition epitopes. J Virol. 1993 Nov;67(11):6866–6871. doi: 10.1128/jvi.67.11.6866-6871.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gairin J. E., Oldstone M. B. Design of high-affinity major histocompatibility complex-specific antagonist peptides that inhibit cytotoxic T-lymphocyte activity: implications for control of viral disease. J Virol. 1992 Nov;66(11):6755–6762. doi: 10.1128/jvi.66.11.6755-6762.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hahn Y. S., Braciale V. L., Braciale T. J. Presentation of viral antigen to class I major histocompatibility complex-restricted cytotoxic T lymphocyte. Recognition of an immunodominant influenza hemagglutinin site by cytotoxic T lymphocyte is independent of the position of the site in the hemagglutinin translation product. J Exp Med. 1991 Sep 1;174(3):733–736. doi: 10.1084/jem.174.3.733. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hahn Y. S., Hahn C. S., Braciale V. L., Braciale T. J., Rice C. M. CD8+ T cell recognition of an endogenously processed epitope is regulated primarily by residues within the epitope. J Exp Med. 1992 Nov 1;176(5):1335–1341. doi: 10.1084/jem.176.5.1335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Jenkins J. R., Rudge K., Redmond S., Wade-Evans A. Cloning and expression analysis of full length mouse cDNA sequences encoding the transformation associated protein p53. Nucleic Acids Res. 1984 Jul 25;12(14):5609–5626. doi: 10.1093/nar/12.14.5609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Klavinskis L. S., Whitton J. L., Joly E., Oldstone M. B. Vaccination and protection from a lethal viral infection: identification, incorporation, and use of a cytotoxic T lymphocyte glycoprotein epitope. Virology. 1990 Oct;178(2):393–400. doi: 10.1016/0042-6822(90)90336-p. [DOI] [PubMed] [Google Scholar]
  19. Lee D. R., Rubocki R. J., Lie W. R., Hansen T. H. The murine MHC class I genes, H-2Dq and H-2Lq, are strikingly homologous to each other, H-2Ld, and two genes reported to encode tumor-specific antigens. J Exp Med. 1988 Nov 1;168(5):1719–1739. doi: 10.1084/jem.168.5.1719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lehmann-Grube F., Ambrassat J. A new method to detect lymphocytic choriomeningitis virus-specific antibody in human sera. J Gen Virol. 1977 Oct;37(1):85–92. doi: 10.1099/0022-1317-37-1-85. [DOI] [PubMed] [Google Scholar]
  21. Lehmann-Grube F., Löhler J., Utermöhlen O., Gegin C. Antiviral immune responses of lymphocytic choriomeningitis virus-infected mice lacking CD8+ T lymphocytes because of disruption of the beta 2-microglobulin gene. J Virol. 1993 Jan;67(1):332–339. doi: 10.1128/jvi.67.1.332-339.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Moskophidis D., Cobbold S. P., Waldmann H., Lehmann-Grube F. Mechanism of recovery from acute virus infection: treatment of lymphocytic choriomeningitis virus-infected mice with monoclonal antibodies reveals that Lyt-2+ T lymphocytes mediate clearance of virus and regulate the antiviral antibody response. J Virol. 1987 Jun;61(6):1867–1874. doi: 10.1128/jvi.61.6.1867-1874.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Noguchi Y., Chen Y. T., Old L. J. A mouse mutant p53 product recognized by CD4+ and CD8+ T cells. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3171–3175. doi: 10.1073/pnas.91.8.3171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Oldstone M. B., Tishon A., Geckeler R., Lewicki H., Whitton J. L. A common antiviral cytotoxic T-lymphocyte epitope for diverse major histocompatibility complex haplotypes: implications for vaccination. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2752–2755. doi: 10.1073/pnas.89.7.2752. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Perkins D. L., Lai M. Z., Smith J. A., Gefter M. L. Identical peptides recognized by MHC class I- and II-restricted T cells. J Exp Med. 1989 Jul 1;170(1):279–289. doi: 10.1084/jem.170.1.279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rammensee H. G., Falk K., Rötzschke O. Peptides naturally presented by MHC class I molecules. Annu Rev Immunol. 1993;11:213–244. doi: 10.1146/annurev.iy.11.040193.001241. [DOI] [PubMed] [Google Scholar]
  27. Rivers T. M., McNair Scott T. F. MENINGITIS IN MAN CAUSED BY A FILTERABLE VIRUS. Science. 1935 May 3;81(2105):439–440. doi: 10.1126/science.81.2105.439-a. [DOI] [PubMed] [Google Scholar]
  28. Romanowski V., Matsuura Y., Bishop D. H. Complete sequence of the S RNA of lymphocytic choriomeningitis virus (WE strain) compared to that of Pichinde arenavirus. Virus Res. 1985 Sep;3(2):101–114. doi: 10.1016/0168-1702(85)90001-2. [DOI] [PubMed] [Google Scholar]
  29. Schulz M., Aichele P., Vollenweider M., Bobe F. W., Cardinaux F., Hengartner H., Zinkernagel R. M. Major histocompatibility complex--dependent T cell epitopes of lymphocytic choriomeningitis virus nucleoprotein and their protective capacity against viral disease. Eur J Immunol. 1989 Sep;19(9):1657–1667. doi: 10.1002/eji.1830190921. [DOI] [PubMed] [Google Scholar]
  30. Weidt G., Utermöhlen O., Zerrahn J., Reimann J., Deppert W., Lehmann-Grube F. CD8+ T lymphocyte-mediated antiviral immunity in mice as a result of injection of recombinant viral proteins. J Immunol. 1994 Sep 15;153(6):2554–2561. [PubMed] [Google Scholar]
  31. Whitton J. L., Sheng N., Oldstone M. B., McKee T. A. A "string-of-beads" vaccine, comprising linked minigenes, confers protection from lethal-dose virus challenge. J Virol. 1993 Jan;67(1):348–352. doi: 10.1128/jvi.67.1.348-352.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Yamnikova S. S., Mandler J., Bekh-Ochir Z. H., Dachtzeren P., Ludwig S., Lvov D. K., Scholtissek C. A reassortant H1N1 influenza A virus caused fatal epizootics among camels in Mongolia. Virology. 1993 Dec;197(2):558–563. doi: 10.1006/viro.1993.1629. [DOI] [PubMed] [Google Scholar]
  33. Zaghouani H., Kuzu Y., Kuzu H., Brumeanu T. D., Swiggard W. J., Steinman R. M., Bona C. A. Contrasting efficacy of presentation by major histocompatibility complex class I and class II products when peptides are administered within a common protein carrier, self immunoglobulin. Eur J Immunol. 1993 Nov;23(11):2746–2750. doi: 10.1002/eji.1830231104. [DOI] [PubMed] [Google Scholar]
  34. Zinkernagel R. M., Welsh R. M. H-2 compatibility requirement for virus-specific T cell-mediated effector functions in vivo. I. Specificity of T cells conferring antiviral protection against lymphocytic choriomeningitis virus is associated with H-2K and H-2D. J Immunol. 1976 Nov;117(5 Pt 1):1495–1502. [PubMed] [Google Scholar]

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