title: 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.affiliation: Program in Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, New York, New York 10016, USA.
authors.forename: Kristina
authors.initials: K
authors.lastname: Somersalo
authors.forename: Nadja
authors.initials: N
authors.lastname: Anikeeva
authors.forename: Tasha N
authors.initials: TN
authors.lastname: Sims
authors.forename: V Kaye
authors.initials: VK
authors.lastname: Thomas
authors.forename: Roland K
authors.initials: RK
authors.lastname: Strong
authors.forename: Thomas
authors.initials: T
authors.lastname: Spies
authors.forename: Tatiana
authors.initials: T
authors.lastname: Lebedeva
authors.forename: Yuri
authors.initials: Y
authors.lastname: Sykulev
authors.forename: Michael L
authors.initials: ML
authors.lastname: Dustin
mesh_terms: D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology*; D002999:Clone Cells; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000276:immunology; D006801:Humans; D018613:Microscopy, Confocal; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology* / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell