Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1172/jci19337

Type

Journal article

Journal

The Journal of clinical investigation

Publication Date

01/2004

Volume

113

Pages

49 - 57

Addresses

Program in Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, New York, New York 10016, USA.

Keywords

Antigen-Presenting Cells, T-Lymphocytes, Helper-Inducer, CD8-Positive T-Lymphocytes, T-Lymphocytes, Cytotoxic, Clone Cells, Humans, Peptide Fragments, Receptors, Antigen, T-Cell, Hemagglutinin Glycoproteins, Influenza Virus, Microscopy, Confocal, Cell Adhesion