Intrathymic Autoantigens and their Role in the Shaping of the Autoimmune T Lymphocyte Repertoire

  • Hartmut Wekerle
  • Monika Bradl
  • Georg Kääb
  • Kimikazu Kojima
  • Christopher Linington
  • Alexander Marx
  • Scott Peterson
  • Markus Reindl


The physical deletion of self-reactive lymphocytes from the immune repertoire is the only way to provide an absolute guarantee for continued maintenance of self tolerance. In fact, deletion of self-reactive T cell clones does occur in the development of the immune repertoire. However, this deletional, self-tolerogenic mechanism is restricted to a limited set of autoantigens, especially those available in the thymus at high concentration. This is not the case for the majority of tissue specific autoantigens, and expression of the autoantigen does not lead to the complete elimination of specific self-reactive T cells. As a consequence all healthy organisms harbor unexpectedly high numbers of self reactive T cells, some of which possess the potential to attack the body’s own tissue and to cause disease.


Myelin Basic Protein Cell Repertoire Immune Repertoire Myelin Basic Protein Gene Thymus Graft 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Ben-Nun, A., Wekerle, H., and Cohen, I.R. (1981). The rapid isolation of clonable antigen-specific T lymphocyte lines capable of mediating autoimmune encephalomyelitis. Eur. J. Immunol. 11, 195–199.PubMedCrossRefGoogle Scholar
  2. 2.
    Bogue, M., Candéias, S., Benoist, C., and Mathis, D. (1991). A special repertoire of a:b T cells in neonatal mice. EMBO J. 10, 3647–3654.PubMedGoogle Scholar
  3. 3.
    Burkly, L.C., Degermann, S., Longley, J., Hagman, J., Brinster, R.L., Lo, D., and Flavell, R.A. (1993). Clonal deletion of Vb5+ T cells by transgenic I-E restricted to thymic medullary epithelium. J. Immunol. 151, 3954–3960.PubMedGoogle Scholar
  4. 4.
    Burns, F.R., Li, X., Shen, N., Offner, H., Chou, Y.K., Vandenbark, A.A., and Heber-Katz, E. (1989). Both rat and mouse T cell receptors specific for the encephalitogenic determinant of myelin basic protein use similar Va and Vb chain genes even though the major histocompatibility complex and encephalitogenic determinants being recognized are different. J. Exp. Med. 169, 27–39.PubMedCrossRefGoogle Scholar
  5. 5.
    Campagnoni, A.T., Pribyl, T.M., Campagnoni, C.W., Kampf, K., Amur-Umarjee, S., Landry, C.F., Handley, V.W., Newman, S.L., Garbay, B., and Kitamura, K. (1993). Structure and developmental regulation of Golli-mbp, a 105 kilobase gene that encompasses the myelin basic protein gene and is expressed in cells in the oligodendrocyte lineage in the brain. J. Biol. Chem. 268, 4930–4938.PubMedGoogle Scholar
  6. 6.
    Chluba, J., Steeg, C., Becker, A., Wekerle, H., and Epplen, J.T. (1989). T cell receptor b chain usage in myelin basic protein-specific rat T lymphocytes. Eur. J. Immunol. 19, 279–284.PubMedCrossRefGoogle Scholar
  7. 7.
    Cohen, I.R. (1992). The cognitive paradigm and the immunological homunculus. Immunol. Today 13, 490–494.PubMedCrossRefGoogle Scholar
  8. 8.
    Feeney, A.J. (1991). Junctional sequences of fetal T cell receptor b chains have few N regions. J. Exp. Med. 174, 115–124.PubMedCrossRefGoogle Scholar
  9. 9.
    Gold, D.P., Offner, H., Sun, D., Wiley, S., Vandenbark, A.A., and Wilson, D.B. (1991). Analysis of T cell receptor b chains in Lewis rats with experimental allergic encephalomyelitis: Conserved complementary determining region 3. J. Exp. Med. 174, 1467–1476.PubMedCrossRefGoogle Scholar
  10. 10.
    Greiner, D.L., Shultz, L.D., Rossini, A.A., Mordes, J.P., Handler, E.S., and Rajan, T.V. (1991). Recapitulation of normal and abnormal BB rat immune system development in SCID mouse/rat lymphohemopoietic chimeras. J. Clin. Invest. 88, 717–719.PubMedCrossRefGoogle Scholar
  11. 11.
    Grima, B., Zelenika, D., and Pessac, B. (1992). A novel transcript overlapping the myelin basic protein gene. J. Neurochem. 59, 2318–2323.PubMedCrossRefGoogle Scholar
  12. 12.
    Jones, R.E., Bourdette, D.N., Whitham, R.H., Offner, H., and Vandenbark, A.A. (1993). Induction of experimental autoimmune encephalomyelitis in severe combined immunodeficient mice reconstituted with allogeneic and xenogeneic hematopoietic cells. J. Immunol. 150, 4620–4629.PubMedGoogle Scholar
  13. 13.
    Jones, R.E., Whitham, R.H., Sullivan, T, Mass, M., and Bourdette, D.N. (1995). Encephalitogenic T lymphocytes develop from SJL/J hematopoietic cells transplanted into severe combined immunodeficient (SCID) mice. J. Neuroimmunol. 57, 155–164.PubMedCrossRefGoogle Scholar
  14. 14.
    Kojima, K., Berger, T., Lassmann, H., Hinze-Selch, D., Zhang, Y, Gehrmann, J., Wekerle, H., and Linington, C. (1994). Experimental autoimmune panencephalitis and uveoretinitis in the Lewis rat transferred by T lymphocytes specific for the S 100b molecule, a calcium binding protein of astroglia. J. Exp. Med. 750, 817–829.CrossRefGoogle Scholar
  15. 15.
    Lannes-Vieira, J., Goudable, B., Drexler, K., Gehrmann, J., Torres-Nagel, N.E., Hünig, T., and Wekerle, H. (1995). Encephalitogenic, myelin basic protein specific T cells from naive rat thymus: Preferential use of the T cell receptor gene Vb8.2 and expression of the CD4CD8 phenotype. Eur. J. Immunol. 25, 611–616.CrossRefGoogle Scholar
  16. 16.
    Lauriola, L., Michetti, F., Stolfi, V.M., Tallini, G., and Cocchia, D. (1984). Detection by S-100 immunolabelling of interdigitating reticulum cells in human thymuses. Virchows Arch. 45, 187–195.CrossRefGoogle Scholar
  17. 17.
    Mathisen, P.M., Pease, S., Garvey, J., Hood, L., and Readhead, C. (1993). Identification of an embryonic isoform of myelin basic protein that is expressed widely in the mouse embryo. Proc. Natl. Acad. Sci. USA 90, 10125–10129.PubMedCrossRefGoogle Scholar
  18. 18.
    Max, H., Haider, T., Kalbus, M., Gnau, V., Jung, G., and Kaibacher, H. (1994). A 16mer peptide of the human autoantigen calreticulin is a most prominent HLA-DR4Dw4 associated self-peptide. Hum. Immunol. 41, 39–45.PubMedCrossRefGoogle Scholar
  19. 19.
    Pribyl, T.M., Campagnoni, C.W., Kampf, K., Kashima, T., Handley, V.W., McMahon, J., and Campagnoni, A.T. (1993). The human myelin basic protein gene is included within a 179-kilobase transcription unit: Expression in the immune and central nervous system. Proc. Natl. Acad. Sei. USA 90, 10695–10699.CrossRefGoogle Scholar
  20. 20.
    Schluesener, H.J. and Wekerle, H. (1985). Autoaggressive T lymphocyte lines recognizing the encephalitogenic region of myelin basic protein: In vitro selection from unprimed rat T lymphocyte populations. J. Immunol. 135, 3128–3133.PubMedGoogle Scholar
  21. 21.
    Surh, C.D. and Sprent, J. (1991). Long-term xenogeneic chimeras. Full differentiation of rat T and B cells in SCID mice. J. Immunol. 147, 2148–2154.Google Scholar
  22. 22.
    Torres-Nagel, N.E., Gold, D.P., and Hünig, T. (1993). Identification of rat Tcrb-V 8.2, 8.5, and 10 gene products by monoclonal antibodies. Immunogenetics 37, 305–308.PubMedCrossRefGoogle Scholar
  23. 23.
    Ushiki, T., Iwanaga, T., Masuda, T., Takahashi, Y., and Fujita, T. (1984). Distribution and ultrastructure of S-100-immunoreactive cells in the human thymus. Cell Tiss. Res. 235, 509–514.Google Scholar
  24. 24.
    Wekerle, H., Kojima, K., Lannes-Vieira, J., Lassmann, H., and Linington, C. (1994). Animal models. Ann. Neurol. 36, S47–S53.PubMedCrossRefGoogle Scholar
  25. 25.
    Zhang, X.-M. and Heber-Katz, E. (1992). T cell receptor sequences from encephalitogenic T cells in adult Lewis rats suggest an early ontogenic origin. J. Immunol. 148, 746–752.PubMedGoogle Scholar
  26. 26.
    Zimmer, D.B., Cornwall, E.H., Landar, A., and Song, W. (1995). The S100 protein family: History, function and expression. Brain Res. Bull. 37, 417–429.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Hartmut Wekerle
    • 1
  • Monika Bradl
    • 1
  • Georg Kääb
    • 1
  • Kimikazu Kojima
    • 1
  • Christopher Linington
    • 1
  • Alexander Marx
    • 1
  • Scott Peterson
    • 1
  • Markus Reindl
    • 1
  1. 1.Max-Planck-Institute of PsychiatryMartinsriedGermany

Personalised recommendations