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The immunological synapse and CD28-CD80 interactions

Nature Immunology volume 2, pages 1159–1166 (2001)Cite this article

Abstract

According to the two-signal model of T cell activation, costimulatory molecules augment T cell receptor (TCR) signaling, whereas adhesion molecules enhance TCR–MHC-peptide recognition. The structure and binding properties of CD28 imply that it may perform both functions, blurring the distinction between adhesion and costimulatory molecules. Our results show that CD28 on naïve T cells does not support adhesion and has little or no capacity for directly enhancing TCR–MHC-peptide interactions. Instead of being dependent on costimulatory signaling, we propose that a key function of the immunological synapse is to generate a cellular microenvironment that favors the interactions of potent secondary signaling molecules, such as CD28.

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Figure 1: Costimulatory effect of GPI-CD80 on transgenic T cell activation.
Figure 2: Naïve T cells do not adhere to CD80 substrates.
Figure 3: CD28-CD80 binding parameters.
Figure 4: Low CD28 mobility regulated by its cytoplasmic tail.
Figure 5: The CD28 cytoplasmic domain of CD28 limited interaction with CD80.
Figure 6: CD28 engagement had no effect on I-Ek or ICAM-1 engagement within the immunological synapse.
Figure 7: CD80 engagement in the central cluster was not required for formation of the immunological synapse.

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Acknowledgements

We thank H. Reiser and M. Naquet for cells producing the 1610A1 and H155 antibodies, respectively; G. Freeman for the mCD80 cDNA;A. Holdorf for Jurkat cells expressing truncation mutants of murine CD28; R. Burack for sharing his unpublished results on cooperation of CD2 and CD28; R. Houdei for cell and antibody production; and R. Barrett for preparation of the manuscript. Supported by funds from the NIH, HHMI, the Whitaker Foundation and Irene Diamond.

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Authors and Affiliations

  1. Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Ave, St. Louis, MO, USA

    Shannon K. Bromley & Andrey S. Shaw

  2. Nuffield Department of Medicine, The University of Oxford, Oxford, UK

    Andrea Iaboni & Simon J. Davis

  3. Biogen Inc, Cambridge, MA

    Adrian Whitty

  4. Department of Medicine, Washington University School of Medicine, 660 S. Euclid Ave, St. Louis, MO, USA

    Jonathan M. Green

  5. Division of Rheumatology, Department of Medicine, Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, CA, USA

    Arthur Weiss & Michael L. Dustin

  6. Department of Pathology and the Program in Molecular Pathogenesis, New York University School of Medicine and The Skirball Institute of Biomolecular Medicine, 540 First Ave, New York, NY, USA

    Michael L. Dustin

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Bromley, S., Iaboni, A., Davis, S. et al. The immunological synapse and CD28-CD80 interactions. Nat Immunol 2, 1159–1166 (2001). https://doi.org/10.1038/ni737

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