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Lymphocyte Activation and Immune Regulation IX pp 191–201Cite as

Regulation of T Cell Migration Through Formation of Immunological Synapses

The Stop Signal Hypothesis

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 512))

Abstract

The antigen specific immune response is initiated by molecular interactions in the nanometer scale gap between the T cell and antigen-presenting cell (APC). This specialized cell-cell junction has been aptly described as an immunological synapse (Norcross, 1984; Paul and Seder, 1994). The immunological synapse is the site of key signaling events that set thresholds for T cell activation. If these thresholds are appropriately set the T cell is defended against a wide array of pathogens and toxins. If these thresholds are incorrectly set the host is susceptible to pathogen escape, at one extreme, and destructive autoimmunity at the other extreme. The immunological synapse is the site of a sensitive molecular search where as few as 10-100 agonist MHC-peptide complexes are sufficient to activate a T cell (Peterson, et al., 1999). The immunological synapse is also the product of an extensive cellular search that brings the T cell and APC together in the secondary lymphoid tissues. The interaction of T cells agonist MHCpeptide complexes on an appropriate surface generates a robust stop signal (Dustin, et al., 1997; Dustin, et al., 1996; Negulescu, et al., 1996). The common characteristic of the stop signal is that the TCR signal appears to control the polarity of the T cell cytoskeleton and maintains a balance of integrin mediated traction forces to hold the T cell in place-an apparently delicate balance (Dustin, et al., 1997). Subsequent studies on the molecular interactions in the immunological synapse reveal a complex signaling landscape in which molecular topology and dynamic assemblies of cytoskeletal molecules and adhesion molecules create distinct supramolecular activation clusters (SMACs) in a bull’s eye pattern (Grakoui, et al., 1999;Monks, et al., 1998). The T cell receptor (TCR) and CD28 occupy the center of the bull’s eye, whereas the adhesion molecules LFA-1 and CD2 occupy the surrounding ring (Bromley, et al., 2001; Grakoui, et al., 1999; Monks, et al., 1998). The immunological synapse is formed through a distinct intermediate in which the6.

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  1. Program in Molecular Pathogenesis and Department of Pathology, Skirball Institute of Molecular Medicine, New York University School of Medicine, 540 First Avenue, 2nd Floor, Labs 4 and 5, New York, NY, 10016, USA

    Michael L. Dustin

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  1. University of California, Irvine, Irvine, California, USA

    Sudhir Gupta

  2. Stanford University School of Medicine, Stanford, California, USA

    Eugene Butcher

  3. National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA

    William Paul

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Dustin, M.L. (2002). Regulation of T Cell Migration Through Formation of Immunological Synapses. In: Gupta, S., Butcher, E., Paul, W. (eds) Lymphocyte Activation and Immune Regulation IX. Advances in Experimental Medicine and Biology, vol 512. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0757-4_25

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