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T-cell clones from a type-1 diabetes patient respond to insulin secretory granule proteins

Abstract

T LYMPHOCYTES reactive to pancreatic β-cells are thought to have a central role in the autoimmune process leading to type 1 (insulin-dependent) diabetes1–6, but the molecular targets of these T cells have not yet been defined. As identification of such antigens may enable measures to be developed to prevent the disease, we have characterized an antigen that is recognized by insulinoma membrane-reactive T-cell clones established from a newly diagnosed type-1 diabetes patient7. Subcellular fractionation studies using rat insulinoma indicate that the antigenic determinant recognized by one of these clones is an integral membrane component of the insulin secretory granule. After a 5,000-fold purification, we have defined the antigen as a monomer of relative molecular mass 38,000. As granular membrane proteins are transiently exposed on the cell surface during exocytosis, their accessibility to components of the immune system may be a function of the secretory activity of β-cells.

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References

  1. Bottazzo, G. F. et al. New Engl. J. Med. 313, 353–360 (1985).

    Article  CAS  Google Scholar 

  2. Stiller, C. R. et al. Science 223, 1362–1367 (1984).

    Article  ADS  CAS  Google Scholar 

  3. Mandrup-Poulsen, T. et al. Lancet i, 599–602 (1989).

    Google Scholar 

  4. Sibley, R. K., Sutherland, D. E. R., Goetz, F. & Michael, A. F. Lab. Invest. 53, 132–144 (1985).

    CAS  PubMed  Google Scholar 

  5. De Berardinis, P. et al. Lancet ii, 823–824 (1988).

    Article  Google Scholar 

  6. Haskins, K., Portas, M., Bergman, B., Lafferty, K. & Bradley, B. Proc. natn. Acad. Sci. U.S.A. 86, 8000–8004 (1989).

    Article  ADS  CAS  Google Scholar 

  7. Van Vliet, E., Roep, B. O., Meulenbroek, L., Bruining, G. J. & De Vries, R. R. P. Eur. J. Immun. 19, 213–216 (1989).

    Article  CAS  Google Scholar 

  8. Guest, P. C., Pipeleers, D., Rossier, J., Rhodes, C. J. & Hutton, J. C. Biochem. J. 264, 503–508 (1989).

    Article  CAS  Google Scholar 

  9. Hutton, J. C., Penn, E. J. & Peshavaria, M. Diabetologia 23, 365–373 (1982).

    Article  CAS  Google Scholar 

  10. Hutton, J. C. Diabetologia 32, 271–281 (1989).

    Article  CAS  Google Scholar 

  11. Day, I. N. M. Molec. cell. Probes 1, 275–295 (1987).

    Article  CAS  Google Scholar 

  12. Sugiura, M. et al. Diab. Res. 3, 111–114 (1986).

    CAS  Google Scholar 

  13. Sugiura, M. et al. Diab. Res. 4, 63–66 (1987).

    CAS  Google Scholar 

  14. Bottazzo, G. F., Florin-Christensen, A. & Doniach, D. Lancet ii, 1279–1283 (1974).

    Article  Google Scholar 

  15. Bruining, G. J., Molenaar, J. L. & Grobbee, D. E. Lancet i, 1100–1103 (1989).

    Article  Google Scholar 

  16. Palmer, J. P. et al. Science 222, 1337–1339 (1983).

    Article  ADS  CAS  Google Scholar 

  17. Baekkeskov, S. et al Nature 298, 167–169 (1982).

    Article  ADS  CAS  Google Scholar 

  18. Powers, P. C., Rabizadeh, A., Akeson, R. & Eisenbarth, G. S. Endocrinology 114, 1338–1343 (1984).

    Article  CAS  Google Scholar 

  19. Prud'homme, G. J., Fuks, A., Colle, E. & Guttman, R. D. Diabetes 33, 801–803 (1984).

    Article  CAS  Google Scholar 

  20. Miller, B. J., Appel, M. C., O'Neil, J. J. & Wicker, L. S. J. Immun. 140, 52–58 (1988).

    CAS  PubMed  Google Scholar 

  21. Charlton, B. & Mandel, T. E. Diabetes 37, 1108–1112 (1988).

    Article  CAS  Google Scholar 

  22. Greiner, D. L. et al. J. exp. Med. 166, 461–475 (1987).

    Article  CAS  Google Scholar 

  23. Dampe, O., Andersson, A., Bjork, E., Hallberg, A. & Karlsson, F. A. Diabetes 38, 1326–1328 (1989).

    Article  Google Scholar 

  24. Gotfredson, C. F., Buschard, K. & Frandsen, E. K. Diabetologia 28, 933–935 (1985).

    Article  Google Scholar 

  25. Acha-Orbea, H. et al. Cell 54, 263–273 (1988).

    Article  CAS  Google Scholar 

  26. Janeway, C. A. Nature 341, 482–483 (1989).

    Article  ADS  CAS  Google Scholar 

  27. Laemmli, U. K. Nature 227, 680–685 (1970).

    Article  ADS  CAS  Google Scholar 

Download references

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Roep, B., Arden, S., de vries, R. et al. T-cell clones from a type-1 diabetes patient respond to insulin secretory granule proteins. Nature 345, 632–634 (1990). https://doi.org/10.1038/345632a0

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