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).
- 2
Demotz, S., Grey, H. M. & Sette, A. Science 249, 1028–1030 (1990).
- 3
Weber, S., Traunecker, A., Oliveri, F., Gerhard, W. & Karjalainen, K. Nature 356, 793–796 (1992).
- 4
Matsui, K. et al. Science 254, 1788–1791 (1991).
- 5
Corr, M. et al. Science 265, 946–949 (1994).
- 6
Sykulev, Y. et al. Immunity 1, 15–22 (1994).
- 7
Krangel, M. S. J. exp. Med. 165, 1141–1159 (1987).
- 8
Minami, Y., Samelson, L. E. & Klausner, R. D. J. biol. Chem. 262, 13342–13347 (1987).
- 9
Cantrell, D. A., Davies, A. A. & Crumpton, M. J. Proc. natn. Acad. Sci. U.S.A. 82, 8158–8162 (1985).
- 10
Luton, F., Buferne, M., Davoust, J., Schmitt-Verhulst, A-M. & Boyer, C. J. Immun. 153, 63–72 (1994).
- 11
Dietrich, J., Hou, X., Wegener, A. M. & Geisler, C. EMBO J. 13, 2156–2166 (1994).
- 12
Padovan, E. et al. Science 262, 422–424 (1993).
- 13
Evavold, B. D., Sloan-Lancaster, J. & Allen, P. M. Immun. Today 14, 602–609 (1993).
- 14
Williams, A. F. & Beyers, A. D. Nature 356, 746–747 (1992).
- 15
Karjalainen, K. Curr. Opin. Immun. 6, 9–12 (1994).
- 16
Sloan-Lancaster, j., Shaw, A. S., Rothbard, J. B. & Allen, P. M. Cell 79, 913–922 (1994).
- 17
Madrenas, J. et al. Science 267, 515–517 (1995).
- 18
Panina, P. et al. Eur. J. Immun. 19, 2237–2242 (1989).
- 19
Valitutti, S. et al. J. exp. Med. 181, 577–584 (1995).
- 20
Clarke, G. R., Reyburn, H., Lancaster, F. C. & Boylston, W. Eur. J. Immun. 24, 837–842 (1994).
- 21
Padovan, E. et al. J. exp. Med. 181, 1587–1591 (1995).
- 22
Lanzavecchia, A., Reid, P. A. & Watts, C. Nature 357, 249–252 (1992).
- 23
Germain, R. N. & Hendrix, L. R. Nature 353, 134–139 (1991).
- 24
Vogt, R. F., Cross, G. D., Henderson, L. O. & Philips, D. L. Cytometry 10, 294–302 (1989).
- 25
Boitel, B. et al. J. exp. Med. 175, 765–777 (1992).
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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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