Abstract
The activation of T cells through interaction of their T-cell receptors with antigenic peptide bound to major histocompatibility complex (MHC) on the surface of antigen presenting cells (APCs) is a crucial step in adaptive immunity. Here we use three-dimensional fluorescence microscopy to visualize individual peptide–I-Ek class II MHC complexes labelled with the phycobiliprotein phycoerythrin in an effort to characterize T-cell sensitivity and the requirements for forming an immunological synapse1,2,3 in single cells. We show that T cells expressing the CD4 antigen respond with transient calcium signalling to even a single agonist peptide–MHC ligand, and that the organization of molecules in the contact zone of the T cell and APC takes on the characteristics of an immunological synapse when only about ten agonists are present. This sensitivity is highly dependant on CD4, because blocking this molecule with antibodies renders T cells unable to detect less than about 30 ligands.
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Acknowledgements
We thank B. Newsome, W. E. Moerner, J. Huppa, L. Wu and P. Ebert for discussions. This work was supported by grants (to M.M.D.) from the NIH and the Howard Hughes Medical Institute. D.J.I. was supported by the Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation Fellowship; M.A.P. was supported by the Howard Hughes Medical Institute; and M.K. was supported by a fellowship from the Alfred Benzon Foundation.
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Irvine, D., Purbhoo, M., Krogsgaard, M. et al. Direct observation of ligand recognition by T cells. Nature 419, 845–849 (2002). https://doi.org/10.1038/nature01076
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DOI: https://doi.org/10.1038/nature01076
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