Cytotoxic T lymphocytes form an antigen-independent ring junction
Kristina Somersalo, … , Yuri Sykulev, Michael L. Dustin
Kristina Somersalo, … , Yuri Sykulev, Michael L. Dustin
Published January 1, 2004
Citation Information: J Clin Invest. 2004;113(1):49-57. https://doi.org/10.1172/JCI19337.
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Article Immunology

Cytotoxic T lymphocytes form an antigen-independent ring junction

Abstract

Immunological synapses are organized cell-cell junctions between T lymphocytes and APCs composed of an adhesion ring, the peripheral supramolecular activation cluster (pSMAC), and a central T cell receptor cluster, the central supramolecular activation cluster (cSMAC). In CD8+ cytotoxic T lymphocytes, the immunological synapse is thought to facilitate specific killing by confining cytotoxic agents to the synaptic cleft. We have investigated the interaction of human CTLs and helper T cells with supported planar bilayers containing ICAM-1. This artificial substrate provides identical ligands to CD4+ and CD8+ T cells, allowing a quantitative comparison. We found that cytotoxic T lymphocytes form a ring junction similar to a pSMAC in response to high surface densities of ICAM-1 in the planar bilayer. MICA, a ligand for NKG2D, facilitated the ring junction formation at lower surface densities of ICAM-1. ICAM-1 and MICA are upregulated in tissues by inflammation- and stress-associated signaling, respectively. Activated CD8+ T cells formed fivefold more ring junctions than did activated CD4+ T cells. The ring junction contained lymphocyte function associated antigen-1 and talin, but did not trigger polarization and granule translocation to the interface. This result has specific implications for the mechanism of effective CTL hunting for antigen in tissues. Abnormalities in this process may alter CTL reactivity.

Authors

Kristina Somersalo, Nadja Anikeeva, Tasha N. Sims, V. Kaye Thomas, Roland K. Strong, Thomas Spies, Tatiana Lebedeva, Yuri Sykulev, Michael L. Dustin

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Figure 6

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Model for IS formation by helper T cells and CTLs. Based on prior report...
Model for IS formation by helper T cells and CTLs. Based on prior reports, the helper T cells migrate on substrates with ICAM-1 (dark gray) alone. When agonist MHCp complexes are encountered, the cells form a nascent IS with ICAM-1 in the center and MHCp complexes (light gray) on the periphery. This pattern then inverts to form the mature IS with ICAM-1 in a ring and MHCp complexes in the center. Based on this study, we propose that CTLs on ICAM-1 alone alternate about four times per hour between ring junctions in which ICAM-1 is organized in a ring and typical migratory morphology. We propose that the CTL ring junction constitutes a functional “presynapse” that intensifies immune surveillance. When antigen is encountered, CTLs form an IS without going through distinct nascent and mature stages. We propose that this “short cut” saves the CTL time and ensures that an adhesive “gasket” is formed before cytolytic substances are released into the synaptic cleft.