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Self tolerance is H–2-restricted

Nature volume 308, pages 738–741 (1984)Cite this article

Abstract

H–2 restriction is an established characteristic of T-cell behaviour1–3 and, in effect, it means that mouse T cells are activated against foreign antigens only if those antigens are presented in a membrane association with molecules of the mouse major histocompatibility complex, H–2. Whether T-cell inactivation or tolerance is also H–2-restricted is a question which has been tested directly4–5 and indirectly6–7 several times in the past. In each case the answer was ‘No’ but in each case the answer was inconclusive. Doubts arose because of the observation that activation of T cells, in vivo, is an H–2-restricted event which appears unrestricted because of antigen processing by the host8–9. If antigen processing is involved in the induction of tolerance, then tolerance might also be an H–2-restricted process disguised to appear unrestricted. We report here a study designed to minimize antigen processing in which we find that T-cell tolerance induction to ‘self’ minor histocompatibility (H) antigens is indeed H–2-restricted.

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References

  1. Zinkernagel, R. M. & Doherty, P. C. Nature 248, 701–702 (1974).

    Article  ADS  CAS  Google Scholar 

  2. Shearer, G. M. Eur. J. Immum. 4, 527–533 (1974).

    Article  CAS  Google Scholar 

  3. Matzinger, P. & Zamoyska, R. Nature 297, 628 (1982).

    Article  ADS  CAS  Google Scholar 

  4. Matzinger, P. & Waterfield, J. D. Nature 285, 492–494 (1980).

    Article  ADS  CAS  Google Scholar 

  5. Lamb, J., Skidmore, B. J., Green, N., Chiller, J. M. & Feldmann, M. J. exp. Med. 157, 1434–1437 (1983).

    Article  CAS  Google Scholar 

  6. Billingham, R. E. & Silvers, W. E. J. Immun., 85, 14–26 (1960).

    CAS  PubMed  Google Scholar 

  7. Von Boehmer, H., Haas, W. & Helmut, P. J. exp. Med. 147, 1291–1295 (1977).

    Article  Google Scholar 

  8. Korngold, R. & Sprent, J. J. exp. Med. 151, 314–327 (1980).

    Article  CAS  Google Scholar 

  9. Matzinger, P. thesis, Univ. California, San Diego (1979).

  10. Cohn, A. & Blomberg, B. Scand. J. Immun. 4, 1–24 (1975).

    Article  CAS  Google Scholar 

  11. Fink, P. J. & Bevan, M. J. J. exp. Med. 148, 766–775 (1978).

    Article  CAS  Google Scholar 

  12. Zinkernagel, R. M. et al. J. exp. Med. 147, 882–896 (1978).

    Article  CAS  Google Scholar 

  13. Matzinger, P. & Mirkwood, G. J. exp. Med. 148, 84–92 (1978).

    Article  CAS  Google Scholar 

  14. Singer, A., Hathcock, K. S. & Hodes, R. J. exp. Med. 155, 339–344 (1982).

    Article  CAS  Google Scholar 

  15. Kruisbeek, A.M., Sharrow, S. O., Mathieson, B.J. & Singer, A. J. Immun. 127, 2168–2176 (1981).

    CAS  PubMed  Google Scholar 

  16. Klein, J. Transplantation 15, 137–153 (1973).

    Article  CAS  Google Scholar 

  17. Flaherty, L. Immunogenetics 3, 533–539 (1976).

    Article  Google Scholar 

  18. Lindahl, K. Immunogenetics 8, 71–76 (1979).

    Article  Google Scholar 

  19. Matzinger, P. & Bevan, M. J. Cell Immun. 29, 1–5 (1977).

    Article  CAS  Google Scholar 

  20. Schwartz, R. H. Scand. J. Immun. 7, 3–10 (1978).

    Article  CAS  Google Scholar 

  21. Matzinger, P. Nature 292, 497–501 (1981).

    Article  ADS  CAS  Google Scholar 

  22. Gotze, D. (ed.) The Major Histocompatibility System in Man and Animals (Springer, Berlin, 1977).

    Google Scholar 

  23. Du Pasquier, L. & Blomberg, B. Immunogenetics 15, 251–260 (1982).

    Article  CAS  Google Scholar 

  24. Jeffreys, A. J. et al. Cell 21, 555–564 (1980).

    Article  CAS  Google Scholar 

  25. Du Pasquier, L. et al. Immunogenetics 5, 129–141 (1977).

    Article  Google Scholar 

  26. Fink, P., Bevan, M. J. & Weissman, I. L. J. exp. Med. (in the press).

  27. Morrissey, P. J., Bradley, D., Sharrow, S. O. & Singer, A. et al. J. exp. Med. 158, 365–377 (1983).

    Article  CAS  Google Scholar 

  28. Groves, E. & Singer, A. J. exp. Med. 158, 1483–1497 (1983).

    Article  CAS  Google Scholar 

Download references

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Author notes

  1. Polly Matzinger

    Present address: Basel Institute for Immunology, Grenzacherstrasse 487, 4005, Basel, Switzerland

Authors and Affiliations

  1. Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB1 2QP, UK

    Polly Matzinger, Rose Zamoyska & Herman Waldmann

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  1. Polly Matzinger
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  2. Rose Zamoyska
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  3. Herman Waldmann
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Matzinger, P., Zamoyska, R. & Waldmann, H. Self tolerance is H–2-restricted. Nature 308, 738–741 (1984). https://doi.org/10.1038/308738a0

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