Abstract
Intracerebral inoculation of susceptible strains of mice with Theiler's murine encephalomyelitis virus (TMEV) results in a chronic, immunologically mediated demyelinating disease that shares many features with human multiple sclerosis. CD4+ T lymphocytes play a critical role in the pathogenesis of virus-induced demyelinating disease. We have identified a region within amino acid residues 24 to 37 of the VP3 capsid protein of TMEV (VP3(24-37)) that is recognized by T lymphocytes from the demyelination-susceptible SJL/J strain of mice. The T-cell response to VP3(24-37) represents a predominant Th-cell response against the virus from either TMEV-immunized or TMEV-infected SJL/J mice, and viral epitopes VP1(233-250), VP2(74-86), and VP3(24-37) account for most of the Th-cell response to TMEV.
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- Allen I., Brankin B. Pathogenesis of multiple sclerosis--the immune diathesis and the role of viruses. J Neuropathol Exp Neurol. 1993 Mar;52(2):95–105. doi: 10.1097/00005072-199303000-00001. [DOI] [PubMed] [Google Scholar]
- Borrow P., Tonks P., Welsh C. J., Nash A. A. The role of CD8+T cells in the acute and chronic phases of Theiler's murine encephalomyelitis virus-induced disease in mice. J Gen Virol. 1992 Jul;73(Pt 7):1861–1865. doi: 10.1099/0022-1317-73-7-1861. [DOI] [PubMed] [Google Scholar]
- Calenoff M. A., Faaberg K. S., Lipton H. L. Genomic regions of neurovirulence and attenuation in Theiler murine encephalomyelitis virus. Proc Natl Acad Sci U S A. 1990 Feb;87(3):978–982. doi: 10.1073/pnas.87.3.978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clatch R. J., Lipton H. L., Miller S. D. Characterization of Theiler's murine encephalomyelitis virus (TMEV)-specific delayed-type hypersensitivity responses in TMEV-induced demyelinating disease: correlation with clinical signs. J Immunol. 1986 Feb 1;136(3):920–927. [PubMed] [Google Scholar]
- 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]
- Dal Canto M. C., Lipton H. L. Multiple sclerosis. Animal model:Theiler's virus infection in mice. Am J Pathol. 1977 Aug;88(2):497–500. [PMC free article] [PubMed] [Google Scholar]
- Dhib-Jalbut S., McFarlin D. E. Immunology of multiple sclerosis. Ann Allergy. 1990 May;64(5):433–444. [PubMed] [Google Scholar]
- 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]
- Francis M. J., Hastings G. Z., Clarke B. E., Brown A. L., Beddell C. R., Rowlands D. J., Brown F. Neutralizing antibodies to all seven serotypes of foot-and-mouth disease virus elicited by synthetic peptides. Immunology. 1990 Feb;69(2):171–176. [PMC free article] [PubMed] [Google Scholar]
- Friedmann A., Frankel G., Lorch Y., Steinman L. Monoclonal anti-I-A antibody reverses chronic paralysis and demyelination in Theiler's virus-infected mice: critical importance of timing of treatment. J Virol. 1987 Mar;61(3):898–903. doi: 10.1128/jvi.61.3.898-903.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gerety S. J., Clatch R. J., Lipton H. L., Goswami R. G., Rundell M. K., Miller S. D. Class II-restricted T cell responses in Theiler's murine encephalomyelitis virus-induced demyelinating disease. IV. Identification of an immunodominant T cell determinant on the N-terminal end of the VP2 capsid protein in susceptible SJL/J mice. J Immunol. 1991 Apr 1;146(7):2401–2408. [PubMed] [Google Scholar]
- Gerety S. J., Karpus W. J., Cubbon A. R., Goswami R. G., Rundell M. K., Peterson J. D., Miller S. D. Class II-restricted T cell responses in Theiler's murine encephalomyelitis virus-induced demyelinating disease. V. Mapping of a dominant immunopathologic VP2 T cell epitope in susceptible SJL/J mice. J Immunol. 1994 Jan 15;152(2):908–918. [PubMed] [Google Scholar]
- Gerety S. J., Rundell M. K., Dal Canto M. C., Miller S. D. Class II-restricted T cell responses in Theiler's murine encephalomyelitis virus-induced demyelinating disease. VI. Potentiation of demyelination with and characterization of an immunopathologic CD4+ T cell line specific for an immunodominant VP2 epitope. J Immunol. 1994 Jan 15;152(2):919–929. [PubMed] [Google Scholar]
- Graham S., Wang E. C., Jenkins O., Borysiewicz L. K. Analysis of the human T-cell response to picornaviruses: identification of T-cell epitopes close to B-cell epitopes in poliovirus. J Virol. 1993 Mar;67(3):1627–1637. doi: 10.1128/jvi.67.3.1627-1637.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Inoue A., Choe Y. K., Kim B. S. Analysis of antibody responses to predominant linear epitopes of Theiler's murine encephalomyelitis virus. J Virol. 1994 May;68(5):3324–3333. doi: 10.1128/jvi.68.5.3324-3333.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kappel C. A., Dal Canto M. C., Melvold R. W., Kim B. S. Hierarchy of effects of the MHC and T cell receptor beta-chain genes in susceptibility to Theiler's murine encephalomyelitis virus-induced demyelinating disease. J Immunol. 1991 Dec 15;147(12):4322–4326. [PubMed] [Google Scholar]
- Kappler J. W., Skidmore B., White J., Marrack P. Antigen-inducible, H-2-restricted, interleukin-2-producing T cell hybridomas. Lack of independent antigen and H-2 recognition. J Exp Med. 1981 May 1;153(5):1198–1214. doi: 10.1084/jem.153.5.1198. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kim B. S., Choe Y. K., Crane M. A., Jue C. R. Identification and localization of a limited number of predominant conformation-independent antibody epitopes of Theiler's murine encephalomyelitus virus. Immunol Lett. 1992 Feb;31(2):199–205. doi: 10.1016/0165-2478(92)90146-f. [DOI] [PubMed] [Google Scholar]
- Leclerc C., Deriaud E., Mimic V., van der Werf S. Identification of a T-cell epitope adjacent to neutralization antigenic site 1 of poliovirus type 1. J Virol. 1991 Feb;65(2):711–718. doi: 10.1128/jvi.65.2.711-718.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lindsley M. D., Rodriguez M. Characterization of the inflammatory response in the central nervous system of mice susceptible or resistant to demyelination by Theiler's virus. J Immunol. 1989 Apr 15;142(8):2677–2682. [PubMed] [Google Scholar]
- Lindsley M. D., Thiemann R., Rodriguez M. Cytotoxic T cells isolated from the central nervous systems of mice infected with Theiler's virus. J Virol. 1991 Dec;65(12):6612–6620. doi: 10.1128/jvi.65.12.6612-6620.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lipton H. L., Friedmann A. Purification of Theiler's murine encephalomyelitis virus and analysis of the structural virion polypeptides: correlation of the polypeptide profile with virulence. J Virol. 1980 Mar;33(3):1165–1172. doi: 10.1128/jvi.33.3.1165-1172.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mahon B. P., Katrak K., Mills K. H. Antigenic sequences of poliovirus recognized by T cells: serotype-specific epitopes on VP1 and VP3 and cross-reactive epitopes on VP4 defined by using CD4+ T-cell clones. J Virol. 1992 Dec;66(12):7012–7020. doi: 10.1128/jvi.66.12.7012-7020.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Melvold R. W., Jokinen D. M., Knobler R. L., Lipton H. L. Variations in genetic control of susceptibility to Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease. I. Differences between susceptible SJL/J and resistant BALB/c strains map near the T cell beta-chain constant gene on chromosome 6. J Immunol. 1987 Mar 1;138(5):1429–1433. [PubMed] [Google Scholar]
- Pena Rossi C., McAllister A., Fiette L., Brahic M. Theiler's virus infection induces a specific cytotoxic T lymphocyte response. Cell Immunol. 1991 Dec;138(2):341–348. doi: 10.1016/0008-8749(91)90158-8. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Rodriguez M., Oleszak E., Leibowitz J. Theiler's murine encephalomyelitis: a model of demyelination and persistence of virus. Crit Rev Immunol. 1987;7(4):325–365. [PubMed] [Google Scholar]
- Roos R. P., Firestone S., Wollmann R., Variakojis D., Arnason B. G. The effect of short-term and chronic immunosuppression on Theiler's virus demyelination. J Neuroimmunol. 1982 Jun;2(3-4):223–234. doi: 10.1016/0165-5728(82)90057-1. [DOI] [PubMed] [Google Scholar]
- Scheu A. K., Cuesta A., Rubio N. Characterization of the immune response to intracerebral inoculation of Theiler's murine encephalomyelitis virus: fine protein specificity of the splenic T cell and humoral antibody response. Immunol Lett. 1989 May;21(2):171–176. doi: 10.1016/0165-2478(89)90055-2. [DOI] [PubMed] [Google Scholar]
- Simons J., Kutubuddin M., Chow M. Characterization of poliovirus-specific T lymphocytes in the peripheral blood of Sabin-vaccinated humans. J Virol. 1993 Mar;67(3):1262–1268. doi: 10.1128/jvi.67.3.1262-1268.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Welsh C. J., Tonks P., Nash A. A., Blakemore W. F. The effect of L3T4 T cell depletion on the pathogenesis of Theiler's murine encephalomyelitis virus infection in CBA mice. J Gen Virol. 1987 Jun;68(Pt 6):1659–1667. doi: 10.1099/0022-1317-68-6-1659. [DOI] [PubMed] [Google Scholar]
- White J., Blackman M., Bill J., Kappler J., Marrack P., Gold D. P., Born W. Two better cell lines for making hybridomas expressing specific T cell receptors. J Immunol. 1989 Sep 15;143(6):1822–1825. [PubMed] [Google Scholar]
- Yauch R. L., Kim B. S. A predominant viral epitope recognized by T cells from the periphery and demyelinating lesions of SJL/J mice infected with Theiler's virus is located within VP1(233-244). J Immunol. 1994 Nov 15;153(10):4508–4519. [PubMed] [Google Scholar]