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. 1997 Jul;71(7):5361–5365. doi: 10.1128/jvi.71.7.5361-5365.1997

Theiler's virus and Mengo virus induce cross-reactive cytotoxic T lymphocytes restricted to the same immunodominant VP2 epitope in C57BL/6 mice.

S Dethlefs 1, N Escriou 1, M Brahic 1, S van der Werf 1, E L Larsson-Sciard 1
PMCID: PMC191774  PMID: 9188606

Abstract

C57BL/6 mice develop a virus-specific cytotoxic T-lymphocyte (CTL) response after intraperitoneal inoculation with either the DA strain of Theiler's virus or Mengo virus, two members of the Cardiovirus genus. These CTLs contribute to viral clearance in the case of Theiler's virus but do not protect the mice from the fatal encephalomyelitis caused by Mengo virus. In this study we show that DA and Mengo virus-induced CTLs are cross-reactive. The cross-reactivity is due to a conserved, H-2Db-restricted epitope located between amino acid residues 122 and 130 of the VP2 capsid protein (VP2(122-130)). This epitope is immunodominant in C57BL/6 mice infected with Theiler's virus. The VP2(122-130) epitope, initially identified for Mengo virus, is the first CTL epitope described for Theiler's virus.

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Selected References

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  1. Aubert C., Chamorro M., Brahic M. Identification of Theiler's virus infected cells in the central nervous system of the mouse during demyelinating disease. Microb Pathog. 1987 Nov;3(5):319–326. doi: 10.1016/0882-4010(87)90002-7. [DOI] [PubMed] [Google Scholar]
  2. Azoulay A., Brahic M., Bureau J. F. FVB mice transgenic for the H-2Db gene become resistant to persistent infection by Theiler's virus. J Virol. 1994 Jun;68(6):4049–4052. doi: 10.1128/jvi.68.6.4049-4052.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Beauverger P., Buckland R., Wild T. F. Measles virus antigens induce both type-specific and canine distemper virus cross-reactive cytotoxic T lymphocytes in mice: localization of a common Ld-restricted nucleoprotein epitope. J Gen Virol. 1993 Nov;74(Pt 11):2357–2363. doi: 10.1099/0022-1317-74-11-2357. [DOI] [PubMed] [Google Scholar]
  4. Beretta A., Ermonval M., Larsson E. L. Degeneracy of H-2 recognition by cytotoxic T lymphocytes: 10% of the total repertoire is "specific" for a given haplotype and up to 1% is self-H-2 reactive. Eur J Immunol. 1986 Jun;16(6):605–609. doi: 10.1002/eji.1830160604. [DOI] [PubMed] [Google Scholar]
  5. Bureau J. F., Montagutelli X., Bihl F., Lefebvre S., Guénet J. L., Brahic M. Mapping loci influencing the persistence of Theiler's virus in the murine central nervous system. Nat Genet. 1993 Sep;5(1):87–91. doi: 10.1038/ng0993-87. [DOI] [PubMed] [Google Scholar]
  6. Bureau J. F., Montagutelli X., Lefebvre S., Guénet J. L., Pla M., Brahic M. The interaction of two groups of murine genes determines the persistence of Theiler's virus in the central nervous system. J Virol. 1992 Aug;66(8):4698–4704. doi: 10.1128/jvi.66.8.4698-4704.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Burrows S. R., Khanna R., Burrows J. M., Moss D. J. An alloresponse in humans is dominated by cytotoxic T lymphocytes (CTL) cross-reactive with a single Epstein-Barr virus CTL epitope: implications for graft-versus-host disease. J Exp Med. 1994 Apr 1;179(4):1155–1161. doi: 10.1084/jem.179.4.1155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Clatch R. J., Melvold R. W., Miller S. D., Lipton H. L. Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease in mice is influenced by the H-2D region: correlation with TEMV-specific delayed-type hypersensitivity. J Immunol. 1985 Aug;135(2):1408–1414. [PubMed] [Google Scholar]
  9. Clatch R. J., Miller S. D., Metzner R., Dal Canto M. C., Lipton H. L. Monocytes/macrophages isolated from the mouse central nervous system contain infectious Theiler's murine encephalomyelitis virus (TMEV). Virology. 1990 May;176(1):244–254. doi: 10.1016/0042-6822(90)90249-q. [DOI] [PubMed] [Google Scholar]
  10. Colter J. S., Campbell J. B., Hatch L. R. The pathogenicity of mice of three variants of Mengo encephalomyelitis virus. J Cell Physiol. 1965 Apr;65(2):229–235. doi: 10.1002/jcp.1030650209. [DOI] [PubMed] [Google Scholar]
  11. Duke G. M., Osorio J. E., Palmenberg A. C. Attenuation of Mengo virus through genetic engineering of the 5' noncoding poly(C) tract. Nature. 1990 Feb 1;343(6257):474–476. doi: 10.1038/343474a0. [DOI] [PubMed] [Google Scholar]
  12. Escriou N., Leclerc C., Gerbard S., Giraud M., van der Werf S. Cytotoxic T cell response to Mengo virus in mice: effector cell phenotype and target proteins. J Gen Virol. 1995 Aug;76(Pt 8):1999–2007. doi: 10.1099/0022-1317-76-8-1999. [DOI] [PubMed] [Google Scholar]
  13. Fiette L., Aubert C., Brahic M., Rossi C. P. Theiler's virus infection of beta 2-microglobulin-deficient mice. J Virol. 1993 Jan;67(1):589–592. doi: 10.1128/jvi.67.1.589-592.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Grant R. A., Filman D. J., Fujinami R. S., Icenogle J. P., Hogle J. M. Three-dimensional structure of Theiler virus. Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2061–2065. doi: 10.1073/pnas.89.6.2061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Henkart P. A. Lymphocyte-mediated cytotoxicity: two pathways and multiple effector molecules. Immunity. 1994 Aug;1(5):343–346. doi: 10.1016/1074-7613(94)90063-9. [DOI] [PubMed] [Google Scholar]
  16. Larsson E. L., Lindahl K. F., Langhorne J., Coutinho A. Quantitative studies on concanavalin A-induced, TCGF-reactive T cells. I. Correlation between proliferation and lectin-dependent cytolytic activity. J Immunol. 1981 Sep;127(3):1081–1085. [PubMed] [Google Scholar]
  17. Lin X., Thiemann N. R., Pease L. R., Rodriguez M. VP1 and VP2 capsid proteins of Theiler's virus are targets of H-2D-restricted cytotoxic lymphocytes in the central nervous system of B10 mice. Virology. 1995 Dec 1;214(1):91–99. doi: 10.1006/viro.1995.9951. [DOI] [PubMed] [Google Scholar]
  18. Lipton H. L., Kratochvil J., Sethi P., Dal Canto M. C. Theiler's virus antigen detected in mouse spinal cord 2 1/2 years after infection. Neurology. 1984 Aug;34(8):1117–1119. doi: 10.1212/wnl.34.8.1117. [DOI] [PubMed] [Google Scholar]
  19. Lipton H. L. Theiler's virus infection in mice: an unusual biphasic disease process leading to demyelination. Infect Immun. 1975 May;11(5):1147–1155. doi: 10.1128/iai.11.5.1147-1155.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Luo M., He C., Toth K. S., Zhang C. X., Lipton H. L. Three-dimensional structure of Theiler murine encephalomyelitis virus (BeAn strain). Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2409–2413. doi: 10.1073/pnas.89.6.2409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nahill S. R., Welsh R. M. High frequency of cross-reactive cytotoxic T lymphocytes elicited during the virus-induced polyclonal cytotoxic T lymphocyte response. J Exp Med. 1993 Feb 1;177(2):317–327. doi: 10.1084/jem.177.2.317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Palmenberg A. C., Osorio J. E. Cardioviral poly(C) tracts and viral pathogenesis. Arch Virol Suppl. 1994;9:67–77. doi: 10.1007/978-3-7091-9326-6_8. [DOI] [PubMed] [Google Scholar]
  23. Pullen L. C., Miller S. D., Dal Canto M. C., Kim B. S. Class I-deficient resistant mice intracerebrally inoculated with Theiler's virus show an increased T cell response to viral antigens and susceptibility to demyelination. Eur J Immunol. 1993 Sep;23(9):2287–2293. doi: 10.1002/eji.1830230935. [DOI] [PubMed] [Google Scholar]
  24. Rammensee H. G., Friede T., Stevanoviíc S. MHC ligands and peptide motifs: first listing. Immunogenetics. 1995;41(4):178–228. doi: 10.1007/BF00172063. [DOI] [PubMed] [Google Scholar]
  25. Rodriguez M., David C. S. Demyelination induced by Theiler's virus: influence of the H-2 haplotype. J Immunol. 1985 Sep;135(3):2145–2148. [PubMed] [Google Scholar]
  26. Rodriguez M., Dunkel A. J., Thiemann R. L., Leibowitz J., Zijlstra M., Jaenisch R. Abrogation of resistance to Theiler's virus-induced demyelination in H-2b mice deficient in beta 2-microglobulin. J Immunol. 1993 Jul 1;151(1):266–276. [PubMed] [Google Scholar]
  27. Rodriguez M., Leibowitz J., David C. S. Susceptibility to Theiler's virus-induced demyelination. Mapping of the gene within the H-2D region. J Exp Med. 1986 Mar 1;163(3):620–631. doi: 10.1084/jem.163.3.620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rodriguez M. Virus-induced demyelination in mice: "dying back" of oligodendrocytes. Mayo Clin Proc. 1985 Jul;60(7):433–438. doi: 10.1016/s0025-6196(12)60865-9. [DOI] [PubMed] [Google Scholar]
  29. Selin L. K., Nahill S. R., Welsh R. M. Cross-reactivities in memory cytotoxic T lymphocyte recognition of heterologous viruses. J Exp Med. 1994 Jun 1;179(6):1933–1943. doi: 10.1084/jem.179.6.1933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Whitton J. L., Tishon A., Lewicki H., Gebhard J., Cook T., Salvato M., Joly E., Oldstone M. B. Molecular analyses of a five-amino-acid cytotoxic T-lymphocyte (CTL) epitope: an immunodominant region which induces nonreciprocal CTL cross-reactivity. J Virol. 1989 Oct;63(10):4303–4310. doi: 10.1128/jvi.63.10.4303-4310.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]

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