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Serial triggering of many T-cell receptors by a few peptide–MHC complexes

Abstract

T LYMPHOCYTES can recognize and be activated by a very small number of complexes of peptide with major histocompatibility complex (MHC) molecules displayed on the surface of antigen-presenting cells (APCs)1,2. The interaction between the T-cell receptor (TCR) and its ligand has low affinity and high off-rate3–6. Both findings suggest that an extremely small number of TCRs must be engaged in interaction with APCs and raise the question of how so few receptors can transduce an activation signal. Here we show that a small number of peptide–MHC complexes can achieve a high TCR occupancy, because a single complex can serially engage and trigger up to 200 TCRs. Furthermore, TCR occupancy is proportional to the T cell's biological response. Our findings suggest that the low affinity of the TCR can be instrumental in enabling a small number of antigenic complexes to be detected.

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References

  1. Harding, C. V. & Unanue, E. R. Nature 346, 574–576 (1990).

    Article  ADS  CAS  Google Scholar 

  2. Demotz, S., Grey, H. M. & Sette, A. Science 249, 1028–1030 (1990).

    Article  ADS  CAS  Google Scholar 

  3. Weber, S., Traunecker, A., Oliveri, F., Gerhard, W. & Karjalainen, K. Nature 356, 793–796 (1992).

    Article  ADS  CAS  Google Scholar 

  4. Matsui, K. et al. Science 254, 1788–1791 (1991).

    Article  ADS  CAS  Google Scholar 

  5. Corr, M. et al. Science 265, 946–949 (1994).

    Article  ADS  CAS  Google Scholar 

  6. Sykulev, Y. et al. Immunity 1, 15–22 (1994).

    Article  CAS  Google Scholar 

  7. Krangel, M. S. J. exp. Med. 165, 1141–1159 (1987).

    Article  CAS  Google Scholar 

  8. Minami, Y., Samelson, L. E. & Klausner, R. D. J. biol. Chem. 262, 13342–13347 (1987).

    CAS  PubMed  Google Scholar 

  9. Cantrell, D. A., Davies, A. A. & Crumpton, M. J. Proc. natn. Acad. Sci. U.S.A. 82, 8158–8162 (1985).

    Article  ADS  CAS  Google Scholar 

  10. Luton, F., Buferne, M., Davoust, J., Schmitt-Verhulst, A-M. & Boyer, C. J. Immun. 153, 63–72 (1994).

    CAS  PubMed  Google Scholar 

  11. Dietrich, J., Hou, X., Wegener, A. M. & Geisler, C. EMBO J. 13, 2156–2166 (1994).

    Article  CAS  Google Scholar 

  12. Padovan, E. et al. Science 262, 422–424 (1993).

    Article  ADS  CAS  Google Scholar 

  13. Evavold, B. D., Sloan-Lancaster, J. & Allen, P. M. Immun. Today 14, 602–609 (1993).

    Article  CAS  Google Scholar 

  14. Williams, A. F. & Beyers, A. D. Nature 356, 746–747 (1992).

    Article  ADS  CAS  Google Scholar 

  15. Karjalainen, K. Curr. Opin. Immun. 6, 9–12 (1994).

    Article  CAS  Google Scholar 

  16. Sloan-Lancaster, j., Shaw, A. S., Rothbard, J. B. & Allen, P. M. Cell 79, 913–922 (1994).

    Article  CAS  Google Scholar 

  17. Madrenas, J. et al. Science 267, 515–517 (1995).

    Article  ADS  CAS  Google Scholar 

  18. Panina, P. et al. Eur. J. Immun. 19, 2237–2242 (1989).

    Article  Google Scholar 

  19. Valitutti, S. et al. J. exp. Med. 181, 577–584 (1995).

    Article  CAS  Google Scholar 

  20. Clarke, G. R., Reyburn, H., Lancaster, F. C. & Boylston, W. Eur. J. Immun. 24, 837–842 (1994).

    Article  CAS  Google Scholar 

  21. Padovan, E. et al. J. exp. Med. 181, 1587–1591 (1995).

    Article  CAS  Google Scholar 

  22. Lanzavecchia, A., Reid, P. A. & Watts, C. Nature 357, 249–252 (1992).

    Article  ADS  CAS  Google Scholar 

  23. Germain, R. N. & Hendrix, L. R. Nature 353, 134–139 (1991).

    Article  ADS  CAS  Google Scholar 

  24. Vogt, R. F., Cross, G. D., Henderson, L. O. & Philips, D. L. Cytometry 10, 294–302 (1989).

    Article  CAS  Google Scholar 

  25. Boitel, B. et al. J. exp. Med. 175, 765–777 (1992).

    Article  CAS  Google Scholar 

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Valitutti, S., Müller, S., Cella, M. et al. Serial triggering of many T-cell receptors by a few peptide–MHC complexes. Nature 375, 148–151 (1995). https://doi.org/10.1038/375148a0

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