Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1989 Aug 1;170(2):355–367. doi: 10.1084/jem.170.2.355

T cell determinants of myelin basic protein include a unique encephalitogenic I-E-restricted epitope for Lewis rats

PMCID: PMC2189414  PMID: 2474052

Abstract

The major encephalitogenic epitope for Lewis rats is the 72-89 sequence of guinea pig basic protein (GP-BP) or rat basic protein (Rt-BP). T cells responsive to this epitope are I-A restricted and preferentially express the V alpha 2:V beta 8 gene combination in their TCR. In this work, we describe for the first time the delayed appearance of T cells specific for additional discrete determinant of BP, the nonencephalitogenic 55-68 sequence of GP-BP restricted by I-A, and the encephalitogenic 87-99 sequence of Rt-BP restricted by I-E. The TCR V alpha 2:V beta 8 gene combination was expressed by both encephalitogenic GP-BP S72-89 and Rt-BP S87-99 T cell specificities but not by GP-BP 44-68-specific T cells. This is the first demonstration of I-E-restricted encephalitogenic T cells in Lewis rats and supports the conclusion that the I-E class II locus is involved in autoimmune diseases.

Full Text

The Full Text of this article is available as a PDF (707.4 KB).

Selected References

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

  1. Babbitt B. P., Allen P. M., Matsueda G., Haber E., Unanue E. R. Binding of immunogenic peptides to Ia histocompatibility molecules. 1985 Sep 26-Oct 2Nature. 317(6035):359–361. doi: 10.1038/317359a0. [DOI] [PubMed] [Google Scholar]
  2. Bourdette D. N., Vandenbark A. A., Hashim G., Whitham R. H., Offner H. T cell lines selected with synthetic peptides are highly encephalitogenic in SJL/J mice. J Neuroimmunol. 1989 May;22(3):255–260. doi: 10.1016/0165-5728(89)90023-4. [DOI] [PubMed] [Google Scholar]
  3. Buus S., Sette A., Colon S. M., Miles C., Grey H. M. The relation between major histocompatibility complex (MHC) restriction and the capacity of Ia to bind immunogenic peptides. Science. 1987 Mar 13;235(4794):1353–1358. doi: 10.1126/science.2435001. [DOI] [PubMed] [Google Scholar]
  4. Chou C. H., Chou F. C., Kowalski T. J., Shapira R., Kibler R. F. The major site of guinea-pig myelin basic protein encephalitogenic in Lewis rats. J Neurochem. 1977 Jan;28(1):115–119. doi: 10.1111/j.1471-4159.1977.tb07716.x. [DOI] [PubMed] [Google Scholar]
  5. Chou Y. K., Vandenbark A. A., Jones R. E., Hashim G., Offner H. Selection of encephalitogenic rat T-lymphocyte clones recognizing an immunodominant epitope on myelin basic protein. J Neurosci Res. 1989 Feb;22(2):181–187. doi: 10.1002/jnr.490220211. [DOI] [PubMed] [Google Scholar]
  6. Davis M. M., Bjorkman P. J. T-cell antigen receptor genes and T-cell recognition. Nature. 1988 Aug 4;334(6181):395–402. doi: 10.1038/334395a0. [DOI] [PubMed] [Google Scholar]
  7. Eylar E. H., Brostoff S., Hashim G., Caccam J., Burnett P. Basic A1 protein of the myelin membrane. The complete amino acid sequence. J Biol Chem. 1971 Sep 25;246(18):5770–5784. [PubMed] [Google Scholar]
  8. Fritz R. B., Skeen M. J., Chou C. H., Garcia M., Egorov I. K. Major histocompatibility complex-linked control of the murine immune response to myelin basic protein. J Immunol. 1985 Apr;134(4):2328–2332. [PubMed] [Google Scholar]
  9. Hashim G. A., Day E. D., Fredane L., Intintola P., Carvalho E. Biological activity of region 65-102 of the myelin basic protein. J Neurosci Res. 1986;16(3):467–478. doi: 10.1002/jnr.490160303. [DOI] [PubMed] [Google Scholar]
  10. Hashim G. A., Sharpe R. D. Experimental allergic encephalomyelitis: structural specificity of determinants for delayed hypersensitivity. Immunochemistry. 1974 Oct;11(10):633–640. doi: 10.1016/0019-2791(74)90220-1. [DOI] [PubMed] [Google Scholar]
  11. Offner H., Brostoff S. W., Vandenbark A. A. Antibodies against I-A and I-E determinants inhibit the activation and function of encephalitogenic T-lymphocyte lines. Cell Immunol. 1986 Jul;100(2):364–373. doi: 10.1016/0008-8749(86)90036-5. [DOI] [PubMed] [Google Scholar]
  12. Offner H., Hashim G. A., Chou Y. K., Celnik B., Jones R., Vandenbark A. A. Encephalitogenic T cell clones with variant receptor specificity. J Immunol. 1988 Dec 1;141(11):3828–3832. [PubMed] [Google Scholar]
  13. Offner H., Hashim G., Vandenbark A. A. Response of rat encephalitogenic T lymphocyte lines to synthetic peptides of myelin basic protein. J Neurosci Res. 1987;17(4):344–348. doi: 10.1002/jnr.490170404. [DOI] [PubMed] [Google Scholar]
  14. Offner H., Standage B. A., Burger D. R., Vandenbark A. A. Delayed type hypersensitivity to gangliosides in the Lewis rat. J Neuroimmunol. 1985 Aug;9(3-4):147–157. doi: 10.1016/s0165-5728(85)80015-1. [DOI] [PubMed] [Google Scholar]
  15. Sakai K., Zamvil S. S., Mitchell D. J., Lim M., Rothbard J. B., Steinman L. Characterization of a major encephalitogenic T cell epitope in SJL/J mice with synthetic oligopeptides of myelin basic protein. J Neuroimmunol. 1988 Aug;19(1-2):21–32. doi: 10.1016/0165-5728(88)90032-x. [DOI] [PubMed] [Google Scholar]
  16. Vandenbark A. A., Gill T., Offner H. A myelin basic protein-specific T lymphocyte line that mediates experimental autoimmune encephalomyelitis. J Immunol. 1985 Jul;135(1):223–228. [PubMed] [Google Scholar]
  17. Vandenbark A. A., Offner H., Reshef T., Fritz R., Chou C. H., Cohen I. R. Specificity of T lymphocyte lines for peptides of myelin basic protein. J Immunol. 1985 Jul;135(1):229–233. [PubMed] [Google Scholar]
  18. Zamvil S. S., Mitchell D. J., Moore A. C., Kitamura K., Steinman L., Rothbard J. B. T-cell epitope of the autoantigen myelin basic protein that induces encephalomyelitis. Nature. 1986 Nov 20;324(6094):258–260. doi: 10.1038/324258a0. [DOI] [PubMed] [Google Scholar]
  19. Zamvil S. S., Mitchell D. J., Powell M. B., Sakai K., Rothbard J. B., Steinman L. Multiple discrete encephalitogenic epitopes of the autoantigen myelin basic protein include a determinant for I-E class II-restricted T cells. J Exp Med. 1988 Sep 1;168(3):1181–1186. doi: 10.1084/jem.168.3.1181. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES