Information transfer at the immunological synapse

Delon, Jérôme; Germain, Ronald N.

doi:10.1016/s0960-9822(00)00870-8

Cited by 139 publications

(102 citation statements)

References 107 publications

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“…Similarly, during antibody responses, long-lasting antigen driven interactions between T helper cells and B cells have been observed in lymph nodes (3). Subsequently, at the contact zone between T cells and APC spatially organized molecular clusters develop, referred to as immune synapse (IS), which is crucial for T-cell activation and effector cells development (4).…”

Section: Immune Synapse Formation Determines Interaction Forces Betwementioning

confidence: 99%

Immune synapse formation determines interaction forces between T cells and antigen-presenting cells measured by atomic force microscopy

Hosseini

Louban

Djandji

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

104

111

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During adaptive immune responses, T lymphocytes recognize antigenic peptides presented by MHC molecules on antigen-presenting cells (APCs). This recognition results in the formation of a so-called immune synapse (IS) at the T-cell/APC interface, which is crucial for T-cell activation. The molecular composition of the IS has been extensively studied, but little is known about the biophysics and interaction forces between T cells and APCs. Here, we report the measurement of interaction forces between T cells and APCs employing atomic force microscopy (AFM). For these investigations, specific T cells were selected that recognize an antigenic peptide presented by MHC-class II molecules on APCs. Dynamic analysis of T-cell/APC interaction by AFM revealed that in the presence of antigen interaction forces increased from 1 to 2 nN at early time-points to a maximum of ≈14 nN after 30 min and decreased again after 60 min. These data correlate with the kinetics of synapse formation that also reached a maximum after 30 min, as determined by high-throughput multispectral imaging flow cytometry. Because the integrin lymphocyte function antigen-1 (LFA-1) and its counterpart intercellular adhesion molecule-1 (ICAM-1) are prominent members of a mature IS, the effect of a small molecular inhibitor for LFA-1, BIRT377, was investigated. BIRT377 almost completely abolish the interaction forces, emphasizing the importance of LFA-1/ICAM-1-interactions for firm T-cell/APC adhesion. In conclusion, using biophysical measurements, this study provides precise values for the interaction forces between T cells and APCs and demonstrates that these forces develop over time and are highest when synapse formation is maximal

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Section: Immune Synapse Formation Determines Interaction Forces Betwementioning

confidence: 99%

Immune synapse formation determines interaction forces between T cells and antigen-presenting cells measured by atomic force microscopy

Hosseini

Louban

Djandji

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

104

111

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“…Although SMACs may not be involved in the delivery of certain very early signals from the TCR (35), a consensus view is emerging postulating that SMACs exist for the purpose of providing a stable signaling platform for the lengthy series of biochemical signals originating from antigen stimulation of the TCR (12,36,37). We postulate that the c-SMAC regulates activation of a subset of TCR-controlled signaling pathways, which require continued TCR signaling following SMAC organization (38).…”

Section: Discussionmentioning

confidence: 99%

Complex and dynamic redistribution of NF-κB signaling intermediates in response to T cell receptor stimulation

Schaefer

Kappler

Kupfer

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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The central zone of the supramolecular activation cluster (c-SMAC) is a zone of T cell receptor (TCR) enrichment that forms at a T cell͞antigen-presenting cell (APC) junction in response to antigen stimulation. We demonstrate that there is a surprisingly complex relocalization process that brings PKC and Bcl10, two intermediates in TCR activation of NF-B, to the cytoplasmic face of the c-SMAC. TCR activation causes enrichment of PKC at the c-SMAC, followed by Bcl10 relocalization to punctate cytoplasmic structures, often at sites distant from the c-SMAC. These Bcl10 structures then undergo further relocalization, becoming enriched at the c-SMAC. TCR activation of NF-B therefore involves the dynamic relocalization of multiple signaling intermediates, with distinct phases proximal to and distant from the c-SMAC.

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“…The prototypical IS is considered as being organized around a c-SMAC (central supramolecular activation cluster) containing the TCR, surrounded by a p-SMAC (peripheral SMAC) [1][2][3][4]; recently the idea of a d-SMAC (distal SMAC) has been added [5]. The distance between the pre-and post-synaptic membranes is expected to be around 15 nm at the c-SMAC, to allow the interactions of 7-nm-high molecules such as the TCR or MHC, and 40-45 nm at the p-SMAC, to fit with the expected space required for integrin-ICAM-1 interactions [6].…”

Section: Introductionmentioning

confidence: 99%

Multifocal structure of the T cell - dendritic cell synapse

et al. 2005

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The structure of immunological synapses formed between murine naive T cells and mature dendritic cells has been subjected to a quantitative analysis. Immunofluorescence images of synapses formed in the absence of antigen show a diffuse synaptic accumulation of CD3 and LFA-1. In electron microscopy, these antigen-free synapses present a number of tight appositions (cleft size *15 nm), all along the synapse. These tight appositions cover a significantly larger surface fraction of antigen-dependent synapses. In immunofluorescence, antigen-dependent synapses show multiple patches of CD3 and LFA-1 with a variable overlap. A similar distribution is observed for PKCh and talin. A concentric organization characteristic of prototypical synapses is rarely observed, even when dendritic cells are paralyzed by cytoskeletal poisons. In T-DC synapses, the interaction surface is composed of several tens of submicronic contact spots, with no large-scale segregation of CD3 and LFA-1. As a comparison, in T-B synapses, a central cluster of CD3 is frequently observed by immunofluorescence, and electron microscopy reveals a central tight apposition. Our data show that it is inappropriate to consider the concentric structure as a "mature synapse" and multifocal structures as immature.

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Information transfer at the immunological synapse

Cited by 139 publications

References 107 publications

Immune synapse formation determines interaction forces between T cells and antigen-presenting cells measured by atomic force microscopy

Immune synapse formation determines interaction forces between T cells and antigen-presenting cells measured by atomic force microscopy

Complex and dynamic redistribution of NF-κB signaling intermediates in response to T cell receptor stimulation

Multifocal structure of the T cell - dendritic cell synapse

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