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. 1997 May;71(5):4181–4185. doi: 10.1128/jvi.71.5.4181-4185.1997

Association between susceptibility to Theiler's virus-induced demyelination and T-cell receptor Jbeta1-Cbeta1 polymorphism rather than Vbeta deletion.

Y Y Bahk 1, C A Kappel 1, G Rasmussen 1, B S Kim 1
PMCID: PMC191580  PMID: 9094705

Abstract

Theiler's murine encephalomyelitis virus (TMEV) induces demyelinating disease in susceptible mouse strains after intracerebral inoculation. The clinical symptoms and histopathology of the central nervous system appear to be similar to those of human multiple sclerosis (MS), and thus, this system provides an excellent infectious animal model for studying MS. The virus-induced demyelination is immune mediated, and the genes involved in the immune response such as those for the T-cell receptor beta-chain and major histocompatibility complex (MHC) haplotypes are known to influence disease susceptibility. To define whether the T-cell receptor Jbeta-Cbeta or Vbeta genes are associated with susceptibility, we have analyzed F2 mice from crosses of susceptible SJL/J (Vbeta(a)-JCbeta(b)) mice and resistant C57L (Vbeta(a)-JCbeta(a)) mice. Our results indicate that susceptibility to TMEV-induced demyelination is associated with restriction fragment length polymorphism reflecting the T-cell receptor Jbeta1-Cbeta1 region rather than the Vbeta polymorphism. This association becomes stronger when the MHC haplotype is considered in the linkage analysis. However, differences in the T-cell receptor alpha-chain haplotype have no significant influence on the pathogenesis of TMEV-induced demyelination.

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Selected References

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  1. Barth R. K., Kim B. S., Lan N. C., Hunkapiller T., Sobieck N., Winoto A., Gershenfeld H., Okada C., Hansburg D., Weissman I. L. The murine T-cell receptor uses a limited repertoire of expressed V beta gene segments. Nature. 1985 Aug 8;316(6028):517–523. doi: 10.1038/316517a0. [DOI] [PubMed] [Google Scholar]
  2. Beall S. S., Concannon P., Charmley P., McFarland H. F., Gatti R. A., Hood L. E., McFarlin D. E., Biddison W. E. The germline repertoire of T cell receptor beta-chain genes in patients with chronic progressive multiple sclerosis. J Neuroimmunol. 1989 Jan;21(1):59–66. doi: 10.1016/0165-5728(89)90159-8. [DOI] [PubMed] [Google Scholar]
  3. Behlke M. A., Chou H. S., Huppi K., Loh D. Y. Murine T-cell receptor mutants with deletions of beta-chain variable region genes. Proc Natl Acad Sci U S A. 1986 Feb;83(3):767–771. doi: 10.1073/pnas.83.3.767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Burns F. R., Li X. B., Shen N., Offner H., Chou Y. K., Vandenbark A. A., Heber-Katz E. Both rat and mouse T cell receptors specific for the encephalitogenic determinant of myelin basic protein use similar V alpha and V beta chain genes even though the major histocompatibility complex and encephalitogenic determinants being recognized are different. J Exp Med. 1989 Jan 1;169(1):27–39. doi: 10.1084/jem.169.1.27. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Candéias S., Waltzinger C., Benoist C., Mathis D. The V beta 17+ T cell repertoire: skewed J beta usage after thymic selection; dissimilar CDR3s in CD4+ versus CD8+ cells. J Exp Med. 1991 Nov 1;174(5):989–1000. doi: 10.1084/jem.174.5.989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Clatch R. J., Lipton H. L., Miller S. D. Class II-restricted T cell responses in Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease. II. Survey of host immune responses and central nervous system virus titers in inbred mouse strains. Microb Pathog. 1987 Nov;3(5):327–337. doi: 10.1016/0882-4010(87)90003-9. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Compston D. A., Kellar Wood H., Robertson N., Sawcer S., Wood N. W. Genes and susceptibility to multiple sclerosis. Acta Neurol Scand Suppl. 1995;161:43–51. doi: 10.1111/j.1600-0404.1995.tb05855.x. [DOI] [PubMed] [Google Scholar]
  9. Dal Canto M. C., Lipton H. L. Primary demyelination in Theiler's virus infection. An ultrastructural study. Lab Invest. 1975 Dec;33(6):626–637. [PubMed] [Google Scholar]
  10. Eastman Q. M., Leu T. M., Schatz D. G. Initiation of V(D)J recombination in vitro obeying the 12/23 rule. Nature. 1996 Mar 7;380(6569):85–88. doi: 10.1038/380085a0. [DOI] [PubMed] [Google Scholar]
  11. Ebers G. C., Kukay K., Bulman D. E., Sadovnick A. D., Rice G., Anderson C., Armstrong H., Cousin K., Bell R. B., Hader W. A full genome search in multiple sclerosis. Nat Genet. 1996 Aug;13(4):472–476. doi: 10.1038/ng0896-472. [DOI] [PubMed] [Google Scholar]
  12. Epstein R., Roehm N., Marrack P., Kappler J., Davis M., Hedrick S., Cohn M. Genetic markers of the antigen-specific T cell receptor locus. J Exp Med. 1985 May 1;161(5):1219–1224. doi: 10.1084/jem.161.5.1219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ferradini L., Gu H., De Smet A., Rajewsky K., Reynaud C. A., Weill J. C. Rearrangement-enhancing element upstream of the mouse immunoglobulin kappa chain J cluster. Science. 1996 Mar 8;271(5254):1416–1420. doi: 10.1126/science.271.5254.1416. [DOI] [PubMed] [Google Scholar]
  14. Garcia K. C., Degano M., Stanfield R. L., Brunmark A., Jackson M. R., Peterson P. A., Teyton L., Wilson I. A. An alphabeta T cell receptor structure at 2.5 A and its orientation in the TCR-MHC complex. Science. 1996 Oct 11;274(5285):209–219. doi: 10.1126/science.274.5285.209. [DOI] [PubMed] [Google Scholar]
  15. Gascoigne N. R., Chien Y., Becker D. M., Kavaler J., Davis M. M. Genomic organization and sequence of T-cell receptor beta-chain constant- and joining-region genes. Nature. 1984 Aug 2;310(5976):387–391. doi: 10.1038/310387a0. [DOI] [PubMed] [Google Scholar]
  16. Haines J. L., Ter-Minassian M., Bazyk A., Gusella J. F., Kim D. J., Terwedow H., Pericak-Vance M. A., Rimmler J. B., Haynes C. S., Roses A. D. A complete genomic screen for multiple sclerosis underscores a role for the major histocompatability complex. The Multiple Sclerosis Genetics Group. Nat Genet. 1996 Aug;13(4):469–471. doi: 10.1038/ng0896-469. [DOI] [PubMed] [Google Scholar]
  17. Haqqi T. M., Banerjee S., Anderson G. D., David C. S. RIII S/J (H-2r). An inbred mouse strain with a massive deletion of T cell receptor V beta genes. J Exp Med. 1989 Jun 1;169(6):1903–1909. doi: 10.1084/jem.169.6.1903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hashimoto L. L., Mak T. W., Ebers G. C. T cell receptor alpha chain polymorphisms in multiple sclerosis. J Neuroimmunol. 1992 Sep;40(1):41–48. doi: 10.1016/0165-5728(92)90211-3. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Kappel C. A., Melvold R. W., Kim B. S. Influence of sex on susceptibility in the Theiler's murine encephalomyelitis virus model for multiple sclerosis. J Neuroimmunol. 1990 Sep-Oct;29(1-3):15–19. doi: 10.1016/0165-5728(90)90143-b. [DOI] [PubMed] [Google Scholar]
  21. Lehrich J. R., Arnason B. G., Hochberg F. H. Demyelinative myelopathy in mice induced by the DA virus. J Neurol Sci. 1976 Oct;29(2-4):149–160. doi: 10.1016/0022-510x(76)90167-2. [DOI] [PubMed] [Google Scholar]
  22. Lipton H. L., Melvold R. Genetic analysis of susceptibility to Theiler's virus-induced demyelinating disease in mice. J Immunol. 1984 Apr;132(4):1821–1825. [PubMed] [Google Scholar]
  23. Marrosu M. G., Muntoni F., Murru M. R., Costa G., Pischedda M. P., Pirastu M., Sotgiu S., Rosati G., Cianchetti C. HLA-DQB1 genotype in Sardinian multiple sclerosis: evidence for a key role of DQB1 *0201 and *0302 alleles. Neurology. 1992 Apr;42(4):883–886. doi: 10.1212/wnl.42.4.883. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Musette P., Bureau J. F., Gachelin G., Kourilsky P., Brahic M. T lymphocyte repertoire in Theiler's virus encephalomyelitis: the nonspecific infiltration of the central nervous system of infected SJL/J mice is associated with a selective local T cell expansion. Eur J Immunol. 1995 Jun;25(6):1589–1593. doi: 10.1002/eji.1830250618. [DOI] [PubMed] [Google Scholar]
  26. Oksenberg J. R., Sherritt M., Begovich A. B., Erlich H. A., Bernard C. C., Cavalli-Sforza L. L., Steinman L. T-cell receptor V alpha and C alpha alleles associated with multiple and myasthenia gravis. Proc Natl Acad Sci U S A. 1989 Feb;86(3):988–992. doi: 10.1073/pnas.86.3.988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Oksenberg J. R., Stuart S., Begovich A. B., Bell R. B., Erlich H. A., Steinman L., Bernard C. C. Limited heterogeneity of rearranged T-cell receptor V alpha transcripts in brains of multiple sclerosis patients. Nature. 1990 May 24;345(6273):344–346. doi: 10.1038/345344a0. [DOI] [PubMed] [Google Scholar]
  28. Oleszak E. L., Kuzmak J., Good R. A., Platsoucas C. D. Immunology of Theiler's murine encephalomyelitis virus infection. Immunol Res. 1995;14(1):13–33. doi: 10.1007/BF02918495. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Rodriguez M., Patick A. K., Pease L. R., David C. S. Role of T cell receptor V beta genes in Theiler's virus-induced demyelination of mice. J Immunol. 1992 Feb 1;148(3):921–927. [PubMed] [Google Scholar]
  31. Rodriguez M., Prayoonwiwat N., Zhou P., David C. Expression of T cell receptor V beta transcripts in central nervous system of mice susceptible and resistant to Theiler's virus-induced demyelination. J Neuroimmunol. 1993 Aug;47(1):95–100. doi: 10.1016/0165-5728(93)90288-a. [DOI] [PubMed] [Google Scholar]
  32. Singer P. A., McEvilly R. J., Balderas R. S., Dixon F. J., Theofilopoulos A. N. T-cell receptor alpha-chain variable-region haplotypes of normal and autoimmune laboratory mouse strains. Proc Natl Acad Sci U S A. 1988 Oct;85(20):7729–7733. doi: 10.1073/pnas.85.20.7729. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Smith L. R., Plaza A., Singer P. A., Theofilopoulos A. N. Coding sequence polymorphisms among V beta T cell receptor genes. J Immunol. 1990 Apr 15;144(8):3234–3237. [PubMed] [Google Scholar]
  34. Utz U., Biddison W. E., McFarland H. F., McFarlin D. E., Flerlage M., Martin R. Skewed T-cell receptor repertoire in genetically identical twins correlates with multiple sclerosis. Nature. 1993 Jul 15;364(6434):243–247. doi: 10.1038/364243a0. [DOI] [PubMed] [Google Scholar]
  35. Wood N. W., Sawcer S. J., Kellar-Wood H. F., Holmans P., Clayton D., Robertson N., Compston D. A. The T-cell receptor beta locus and susceptibility to multiple sclerosis. Neurology. 1995 Oct;45(10):1859–1863. doi: 10.1212/wnl.45.10.1859. [DOI] [PubMed] [Google Scholar]
  36. Wucherpfennig K. W., Ota K., Endo N., Seidman J. G., Rosenzweig A., Weiner H. L., Hafler D. A. Shared human T cell receptor V beta usage to immunodominant regions of myelin basic protein. Science. 1990 May 25;248(4958):1016–1019. doi: 10.1126/science.1693015. [DOI] [PubMed] [Google Scholar]
  37. Yauch R. L., Kerekes K., Saujani K., Kim B. S. Identification of a major T-cell epitope within VP3 amino acid residues 24 to 37 of Theiler's virus in demyelination-susceptible SJL/J mice. J Virol. 1995 Nov;69(11):7315–7318. doi: 10.1128/jvi.69.11.7315-7318.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. 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]
  39. Zamvil S. S., Mitchell D. J., Lee N. E., Moore A. C., Waldor M. K., Sakai K., Rothbard J. B., McDevitt H. O., Steinman L., Acha-Orbea H. Predominant expression of a T cell receptor V beta gene subfamily in autoimmune encephalomyelitis. J Exp Med. 1988 May 1;167(5):1586–1596. doi: 10.1084/jem.167.5.1586. [DOI] [PMC free article] [PubMed] [Google Scholar]

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