Letter | Published:

Spreading of T-cell autoimmunity to cryptic determinants of an autoantigen

Nature volume 358, pages 155157 (09 July 1992) | Download Citation

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Abstract

IMMUNIZATION with myelin basic protein (MBP) induces experimental allergic encephalomyelitis (EAE), a prototype of CD4+ T-cell mediated autoimmune disease. In rodents, MBP-reactive T-cell clones are specific for a single, dominant determinant on MBP and use a highly restricted number of T-cell receptor genes1–3. Accordingly, EAE has been prevented by various receptor-specific treatments1–8, suggesting similar strategies may be useful for therapy of human autoimmune disease. Here we report that in (SJL x B 10.PL)F1 mice, immune dominance of a single determinant, MBP: Ac1–11, is confined to the inductive phase of EAE. In mice with chronic EAE, several additional determinants of MBP in peptides 35–47, 81–100 and 121–140 recall proliferative responses. Most importantly, reactivity to the latter determinants was also detected after induction of EAE with MBP peptide Ac1–11 alone; this demonstrates priming by endogenous MBP determinants. Thus, determinants of MBP that are cryptic9–11 after primary immunization can become immunogenic in the course of EAE. Diversification of the autoreactive T-cell repertoire due to 'determinant spreading' has major implications for the pathogenesis of, and the therapeutic approach to, T-cell driven autoimmune disease.

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References

  1. 1.

    et al. Cell 54, 577–592 (1988).

  2. 2.

    et al. Cell 54, 263–273 (1988).

  3. 3.

    & J. exp. Med. 168, 2153–2164 (1988).

  4. 4.

    , & Nature 292, 60–61 (1981).

  5. 5.

    , & Nature 341, 541–544 (1989).

  6. 6.

    et al. Science 246, 668–670 (1989).

  7. 7.

    , & Science 251, 430–432 (1991).

  8. 8.

    , & J. exp. Med. 171, 1943–1955 (1990).

  9. 9.

    & Nature 342, 183–185 (1989).

  10. 10.

    et al. J. exp. Med. 172, 1341–1346 (1990).

  11. 11.

    , & Immun. Today 12, 193–195 (1991).

  12. 12.

    & J. exp. Med. 155, 31–40 (1982).

  13. 13.

    et al. J. Neuroimmun. 19, 21–32 (1988).

  14. 14.

    et al. Cold Spring Harb. Symp. quant. molec. Biol. 54, 859–874 (1989).

  15. 15.

    et al. J. exp. Med. 168, 1181–1186 (1988).

  16. 16.

    & J. Immun. 138, 1434–1441 (1987).

  17. 17.

    , & J. Neuroimmun. 33, 7–15 (1991).

  18. 18.

    , & J. Neuroimmun. 29, 73–79 (1990).

  19. 19.

    Nature 346, 844–847 (1990).

  20. 20.

    & Immun. Today 10, 164–169 (1989).

  21. 21.

    & in Chem. Immun. 46, 101–125 (1989).

  22. 22.

    , & Prep. Biochem. 2, 139–165 (1972).

  23. 23.

    & in Synthetic Peptides in Biology and Medicine (eds Alitalo, K., Partonen, P. & Vahen, A.) 29–42 (Elsevier, Amsterdam, 1985).

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  1. Department of Microbiology and Molecular Genetics, University of California at Los Angeles, 405 Hilgard Avenue, Los Angeles, California 90024, USA

    • Paul V. Lehmann
    • , Thomas Forsthuber
    • , Alexander Miller
    •  & Eli E. Sercarz

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https://doi.org/10.1038/358155a0

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