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T cell killing does not require the formation of a stable mature immunological synapse

Nature Immunology volume 5, pages 524–530 (2004)Cite this article

A Corrigendum to this article was published on 01 June 2004

Abstract

A notable feature of T lymphocyte recognition on other cell surfaces is the formation of a stable mature immunological synapse. Here we use a single-molecule labeling method to directly measure the number of ligands a cytotoxic T cell engages and track the consequences of that interaction by three-dimensional video microscopy. Like helper T cells, cytotoxic T cells were able to detect even a single foreign antigen but required about ten complexes of peptide–major histocompatibility complex (pMHC) to achieve full calcium increase and to form a mature synapse. Thus, cytotoxic T cells and helper T cells are more uniform in their antigen sensitivities than previously thought. Furthermore, only three pMHC complexes were required for killing, showing that stable synapse formation and complete signaling are not required for cytotoxicity.

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Figure 1: Both 2C and OT-1 CTLs recognize wild-type and extended (and biotinylated) antigen-MHC complexes with equal efficacy.
Figure 2: Dose response of T cell calcium signals to antigenic pMHC complexes in the T cell–APC interface.
Figure 3: Correlation of cytotoxicity with spatial distribution of pMHC complexes at the immunological synapse.
Figure 4: Distribution of antigen receptors and signal transduction components at the MHC class I–restricted immunological synapse.
Figure 5: Antigen-induced clustering of H-2Kb(D227K) in presence of wild-type H-2Kb.

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Acknowledgements

We thank J. Chen and H. Eisen for the 2C cytotoxic T cell clone and M.S. Kuhns for providing the pMSCV-Z4 retroviral vector. Supported by the National Institutes of Health (M.M.D.), Howard Hughes Medical Institute (M.A.P.), Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation Fellowship (D.J.I.) and Cancer Research Institute (J.B.H.).

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  1. Darrell J Irvine

    Present address: Department of Material Science & Engineering/Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA

Authors and Affiliations

  1. The Department of Microbiology and Immunology and the Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, 94305, California, USA

    Marco A Purbhoo, Darrell J Irvine, Johannes B Huppa & Mark M Davis

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Correspondence to Mark M Davis.

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Purbhoo, M., Irvine, D., Huppa, J. et al. T cell killing does not require the formation of a stable mature immunological synapse. Nat Immunol 5, 524–530 (2004). https://doi.org/10.1038/ni1058

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