Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1995 Jun 20;92(13):5850–5854. doi: 10.1073/pnas.92.13.5850

T-cell receptor (TCR) usage in Lewis rat experimental autoimmune encephalomyelitis: TCR beta-chain-variable-region V beta 8.2-positive T cells are not essential for induction and course of disease.

R Gold 1, G Giegerich 1, H P Hartung 1, K V Toyka 1
PMCID: PMC41599  PMID: 7597040

Abstract

Predominant usage of V beta 8.2 gene segments, encoding a T-cell receptor (TCR) beta chain variable region, has been reported for pathogenic Lewis rat T cells reactive to myelin basic protein (MBP). However, up to 75% of the alpha/beta T cells in a panel of MBP-specific T-cell lines did not display TCR V beta 8.2, V beta 8.5, V beta 10, or V beta 16 elements. To further investigate TCR usage, we sorted the T-cell lines for V beta 8.2- and V beta 10-positive T cells or depleted the lines of cells with these TCRs. V beta 8.2-positive T cells and one of the depleted T-cell lines strongly reacted against the MBP peptide MBP-(68-88). The depleted T-cell line caused marked experimental autoimmune encephalomyelitis (EAE) even in Lewis rats in which endogenous V beta 8.2-positive T cells had been eliminated by neonatal treatment with anti-V beta 8.2 monoclonal antibodies. T-cell hybridomas generated from this line predominantly used V beta 3 TCR genes coexpressed with TCR V alpha 2 transcripts, which were also used by V beta 8.2-positive T cells. Furthermore, V beta 10-positive T cells reactive to MBP-(44-67) were encephalitogenic when injected immediately after positive selection. After induction of EAE by sorted V beta 8.2- or V beta 10-positive T-cell lines, immunocytochemical analysis of the spinal cord tissue showed a predominance of the injected TCR or of nontypable alpha/beta T cells after injection of the depleted line. Our results demonstrate heterogeneity of TCR beta-chain usage even for a single autoantigen in an inbred strain. Moreover, V beta 8.2-positive T cells are not essential for the induction and progression of adoptive-transfer EAE.

Full text

PDF
5850

Images in this article

5853Fig. 4
on p.5853
5853Fig. 5
on p.5853

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Broeren C. P., Verjans G. M., Van Eden W., Kusters J. G., Lenstra J. A., Logtenberg T. Conserved nucleotide sequences at the 5' end of T cell receptor variable genes facilitate polymerase chain reaction amplification. Eur J Immunol. 1991 Mar;21(3):569–575. doi: 10.1002/eji.1830210306. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Chluba J., Steeg C., Becker A., Wekerle H., Epplen J. T. T cell receptor beta chain usage in myelin basic protein-specific rat T lymphocytes. Eur J Immunol. 1989 Feb;19(2):279–284. doi: 10.1002/eji.1830190210. [DOI] [PubMed] [Google Scholar]
  4. Cross A. H., Cannella B., Brosnan C. F., Raine C. S. Homing to central nervous system vasculature by antigen-specific lymphocytes. I. Localization of 14C-labeled cells during acute, chronic, and relapsing experimental allergic encephalomyelitis. Lab Invest. 1990 Aug;63(2):162–170. [PubMed] [Google Scholar]
  5. Gehrmann J., Gold R., Linington C., Lannes-Vieira J., Wekerle H., Kreutzberg G. W. Spinal cord microglia in experimental allergic neuritis. Evidence for fast and remote activation. Lab Invest. 1992 Jul;67(1):100–113. [PubMed] [Google Scholar]
  6. Gold D. P., Vainiene M., Celnik B., Wiley S., Gibbs C., Hashim G. A., Vandenbark A. A., Offner H. Characterization of the immune response to a secondary encephalitogenic epitope of basic protein in Lewis rats. II. Biased T cell receptor V beta expression predominates in spinal cord infiltrating T cells. J Immunol. 1992 Mar 15;148(6):1712–1717. [PubMed] [Google Scholar]
  7. Happ M. P., Heber-Katz E. Differences in the repertoire of the Lewis rat T cell response to self and non-self myelin basic proteins. J Exp Med. 1988 Feb 1;167(2):502–513. doi: 10.1084/jem.167.2.502. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hinkkanen A. E., Mättä J., Qin Y. F., Linington C., Salmi A., Wekerle H. Novel Tcr Tcra-V and -J transcripts expressed in rat myelin-specific T-cell lines. Immunogenetics. 1993;37(3):235–238. doi: 10.1007/BF00191892. [DOI] [PubMed] [Google Scholar]
  9. Howell M. D., Winters S. T., Olee T., Powell H. C., Carlo D. J., Brostoff S. W. Vaccination against experimental allergic encephalomyelitis with T cell receptor peptides. Science. 1989 Nov 3;246(4930):668–670. doi: 10.1126/science.2814489. [DOI] [PubMed] [Google Scholar]
  10. Hünig T., Wallny H. J., Hartley J. K., Lawetzky A., Tiefenthaler G. A monoclonal antibody to a constant determinant of the rat T cell antigen receptor that induces T cell activation. Differential reactivity with subsets of immature and mature T lymphocytes. J Exp Med. 1989 Jan 1;169(1):73–86. doi: 10.1084/jem.169.1.73. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Joosten I., Wauben M. H., Holewijn M. C., Reske K., Pedersen L. O., Roosenboom C. F., Hensen E. J., van Eden W., Buus S. Direct binding of autoimmune disease related T cell epitopes to purified Lewis rat MHC class II molecules. Int Immunol. 1994 May;6(5):751–759. doi: 10.1093/intimm/6.5.751. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Karin N., Szafer F., Mitchell D., Gold D. P., Steinman L. Selective and nonselective stages in homing of T lymphocytes to the central nervous system during experimental allergic encephalomyelitis. J Immunol. 1993 May 1;150(9):4116–4124. [PubMed] [Google Scholar]
  13. Lannes-Vieira J., Gehrmann J., Kreutzberg G. W., Wekerle H. The inflammatory lesion of T cell line transferred experimental autoimmune encephalomyelitis of the Lewis rat: distinct nature of parenchymal and perivascular infiltrates. Acta Neuropathol. 1994;87(5):435–442. doi: 10.1007/BF00294169. [DOI] [PubMed] [Google Scholar]
  14. Mannie M. D., Paterson P. Y., U'Prichard D. C., Flouret G. Induction of experimental allergic encephalomyelitis in Lewis rats with purified synthetic peptides: delineation of antigenic determinants for encephalitogenicity, in vitro activation of cellular transfer, and proliferation of lymphocytes. Proc Natl Acad Sci U S A. 1985 Aug;82(16):5515–5519. doi: 10.1073/pnas.82.16.5515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Miltenyi S., Müller W., Weichel W., Radbruch A. High gradient magnetic cell separation with MACS. Cytometry. 1990;11(2):231–238. doi: 10.1002/cyto.990110203. [DOI] [PubMed] [Google Scholar]
  16. Morris M., Barclay A. N., Williams A. F. Analysis of T cell receptor beta chains in rat thymus, and rat C alpha and C beta sequences. Immunogenetics. 1988;27(3):174–179. doi: 10.1007/BF00346583. [DOI] [PubMed] [Google Scholar]
  17. Offner H., Buenafe A. C., Vainiene M., Celnik B., Weinberg A. D., Gold D. P., Hashim G., Vandenbark A. A. Where, when, and how to detect biased expression of disease-relevant V beta genes in rats with experimental autoimmune encephalomyelitis. J Immunol. 1993 Jul 1;151(1):506–517. [PubMed] [Google Scholar]
  18. Offner H., Hashim G. A., Celnik B., Galang A., Li X. B., Burns F. R., Shen N., Heber-Katz E., Vandenbark A. A. T cell determinants of myelin basic protein include a unique encephalitogenic I-E-restricted epitope for Lewis rats. J Exp Med. 1989 Aug 1;170(2):355–367. doi: 10.1084/jem.170.2.355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Offner H., Hashim G. A., Vandenbark A. A. T cell receptor peptide therapy triggers autoregulation of experimental encephalomyelitis. Science. 1991 Jan 25;251(4992):430–432. doi: 10.1126/science.1989076. [DOI] [PubMed] [Google Scholar]
  20. Offner H., Vainiene M., Gold D. P., Celnik B., Wang R., Hashim G. A., Vandenbark A. A. Characterization of the immune response to a secondary encephalitogenic epitope of basic protein in Lewis rats. I. T cell receptor peptide regulation of T cell clones expressing cross-reactive V beta genes. J Immunol. 1992 Mar 15;148(6):1706–1711. [PubMed] [Google Scholar]
  21. Schluesener H., Brunner C., Vass K., Lassmann H. Therapy of rat autoimmune disease by a monoclonal antibody specific for T lymphoblasts. J Immunol. 1986 Dec 15;137(12):3814–3820. [PubMed] [Google Scholar]
  22. Shirwan H., Ohanjanian M., Burcham G., Makowka L., Cramer D. V. Structure and diversity of rat T cell receptor alpha-chain genes. J Immunol. 1993 Mar 15;150(6):2295–2304. [PubMed] [Google Scholar]
  23. Smith L. R., Kono D. H., Kammuller M. E., Balderas R. S., Theofilopoulos A. N. V beta repertoire in rats and implications for endogenous superantigens. Eur J Immunol. 1992 Mar;22(3):641–645. doi: 10.1002/eji.1830220305. [DOI] [PubMed] [Google Scholar]
  24. Smith L. R., Kono D. H., Theofilopoulos A. N. Complexity and sequence identification of 24 rat V beta genes. J Immunol. 1991 Jul 1;147(1):375–379. [PubMed] [Google Scholar]
  25. Stangel M., Giegerich G., Torres-Nagel N. E., Hünig T., Hartung H. P. Structural analysis of the rat T-cell receptor Tcra V4 gene family. Immunogenetics. 1995;41(2-3):125–130. doi: 10.1007/BF00182323. [DOI] [PubMed] [Google Scholar]
  26. Sun D., Gold D. P., Smith L., Brostoff S., Coleclough C. Characterization of rat encephalitogenic T cells bearing non-V beta 8 T cell receptors. Eur J Immunol. 1992 Feb;22(2):591–594. doi: 10.1002/eji.1830220244. [DOI] [PubMed] [Google Scholar]
  27. Sun D., Hu X. Z., Le J., Swanborg R. H. Characterization of brain-isolated rat encephalitogenic T cell lines. Eur J Immunol. 1994 Jun;24(6):1359–1364. doi: 10.1002/eji.1830240618. [DOI] [PubMed] [Google Scholar]
  28. Sun D., Le J., Coleclough C. Diverse T cell receptor beta chain usage by rat encephalitogenic T cells reactive to residues 68-88 of myelin basic protein. Eur J Immunol. 1993 Feb;23(2):494–498. doi: 10.1002/eji.1830230229. [DOI] [PubMed] [Google Scholar]
  29. Torres-Nagel N. E., Giegerich G., Gold D. P., Hünig T. Identification of rat Tcra-V 4 and 8 gene products by monoclonal antibodies and cDNA sequence. Immunogenetics. 1994;39(5):367–370. doi: 10.1007/BF00189236. [DOI] [PubMed] [Google Scholar]
  30. Tsuchida M., Matsumoto Y., Hirahara H., Hanawa H., Tomiyama K., Abo T. Preferential distribution of V beta 8.2-positive T cells in the central nervous system of rats with myelin basic protein-induced autoimmune encephalomyelitis. Eur J Immunol. 1993 Oct;23(10):2399–2406. doi: 10.1002/eji.1830231004. [DOI] [PubMed] [Google Scholar]
  31. Vandenbark A. A., Hashim G., Offner H. Immunization with a synthetic T-cell receptor V-region peptide protects against experimental autoimmune encephalomyelitis. Nature. 1989 Oct 12;341(6242):541–544. doi: 10.1038/341541a0. [DOI] [PubMed] [Google Scholar]
  32. Wilson R. K., Lai E., Concannon P., Barth R. K., Hood L. E. Structure, organization and polymorphism of murine and human T-cell receptor alpha and beta chain gene families. Immunol Rev. 1988 Jan;101:149–172. doi: 10.1111/j.1600-065x.1988.tb00736.x. [DOI] [PubMed] [Google Scholar]
  33. Zhao M. L., Xia J. Q., Fritz R. B. Experimental allergic encephalomyelitis in susceptible and resistant strains of mice after adoptive transfer of T cells activated by antibodies to the T cell receptor complex. J Neuroimmunol. 1992 Sep;40(1):31–39. doi: 10.1016/0165-5728(92)90210-c. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES