T‐cell receptor signaling to integrins

Burbach, Brandon J.; Medeiros, Ricardo B.; Mueller, Kristen L.; Shimizu, Yoji

doi:10.1111/j.1600-065x.2007.00527.x

Cited by 130 publications

(112 citation statements)

References 163 publications

(281 reference statements)

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“…Previous work showed that tetraspanins stabilize integrins in their active conformations [13] and that CD9 promotes β1 activation [14]. Activation of LFA-1 integrin is regulated by the actin linker protein talin [15], which has been implicated in integrin "inside-out" signaling [16]. However, talin relocalization to the IS in CD9-and CD151-silenced T cells remained similar to control cells (Supporting Information Fig.…”

mentioning

confidence: 81%

Tetraspanins CD9 and CD151 at the immune synapse support T‐cell integrin signaling

et al. 2014

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Understanding how the immune response is activated and amplified requires detailed knowledge of the stages in the formation of the immunological synapse (IS) between T lymphocytes and antigen-presenting cells (APCs). We show that tetraspanins CD9 and CD151 congregate at the T-cell side of the IS. Silencing of CD9 or CD151 blunts the IL-2 secretion and expression of the activation marker CD69 by APC-conjugated T lymphocytes, but does not affect the accumulation of CD3 or actin to the IS, or the translocation of the microtubule-organizing center toward the T-B contact area. CD9 or CD151 silencing diminishes the relocalization of α4β1 integrin to the IS and reduces the accumulation of high-affinity β1 integrins at the cell-cell contact. These changes are accompanied by diminished phosphorylation of the integrin downstream targets FAK and ERK1/2. Our results suggest that CD9 and CD151 support integrin-mediated signaling at the IS.Keywords: CD9 r CD151 r Immune synapse r Integrins r T-cell activation Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionInteraction between T lymphocytes and antigen-presenting cells (APCs) is critical for antigen presentation and for the initiation of the immune response. This process is characterized by the formation of a dynamic structure called the immune synapse (IS) at the contact between T cells and APCs [1]. At the T cell side of the IS, T-cell receptors (TCRs) and Correspondence: Dr.Francisco Sánchez-Madrid e-mail: fsmadrid@salud.madrid.org associated molecules accumulate in the central area (central supramolecular activation cluster; cSMAC), while adhesion receptors and integrins reorganize in a surrounding external ring called peripheral SMAC (pSMAC) [1]. The increased IS stability enhances T-cell sensitivity, stimulates cytoskeletal processes, induces downstream signaling, and drives effective T-cell differentiation [2,3]. How integrins regulate these processes is not fully understood.Several membrane receptors and integrins concentrated at the IS -CD3, CD4, ICAM-1, lymphocyte function-associated antigen 1 (LFA-1), and very late antigen 4 (VLA-4) -are associated with tetraspanins [4,5] 1968 Rocha-Perugini Vera et al. Eur. J. Immunol. 2014. 44: 1967-1975 organize membrane macrocomplexes called tetraspanin-enriched microdomains (TEMs) [6]. Tetraspanins modulate the function of their associated partners and play important roles in immunity, inflammation, and other processes [6]. Tetraspanins that accumulate at the IS include CD81, which regulates IS architectural organization and maturation [5], and CD82, which contributes to T-cell activation through Rho GTPase-dependent regulation of the actin cytoskeleton [7]. CD82 also increases the adhesion of LFA-1 integrin to its ligand ICAM-1 expressed on APCs [4]. The tetraspanins CD81, CD82, CD53, and CD9 provide T cell costimulatory signals, and CD9 localizes together with TCR signaling molecules in lipid microdomains [4]. Moreover, the T cells of mice deficien...

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confidence: 81%

Tetraspanins CD9 and CD151 at the immune synapse support T‐cell integrin signaling

et al. 2014

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“…This implies that under physiologic settings, lymphocytes may employ ILPs as discrete subcellular '3D-reaction volumes' with 'signalosome'-like properties that amplify and sustain signaling by concentrating important molecules/activities 32,33 . Additionally, the presence of significant biomechanical inputs (i.e., cell-cell force application) at sights if ILP protrusion against the APC can be inferred from the imaging.…”

Section: Discussionmentioning

confidence: 99%

An Endothelial Planar Cell Model for Imaging Immunological Synapse Dynamics

Martinelli

Carman

2015

JoVE

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Adaptive immunity is regulated by dynamic interactions between T cells and antigen presenting cells ('APCs') referred to as 'immunological synapses'. Within these intimate cell-cell interfaces discrete sub-cellular clusters of MHC/Ag-TCR, F-actin, adhesion and signaling molecules form and remodel rapidly. These dynamics are thought to be critical determinants of both the efficiency and quality of the immune responses that develop and therefore of protective versus pathologic immunity. Current understanding of immunological synapses with physiologic APCs is limited by the inadequacy of the obtainable imaging resolution. Though artificial substrate models (e.g., planar lipid bilayers) offer excellent resolution and have been extremely valuable tools, they are inherently non-physiologic and oversimplified. Vascular and lymphatic endothelial cells have emerged as an important peripheral tissue (or stromal) compartment of 'semi-professional APCs'. These APCs (which express most of the molecular machinery of professional APCs) have the unique feature of forming virtually planar cell surface and are readily transfectable (e.g., with fluorescent protein reporters). Herein a basic approach to implement endothelial cells as a novel and physiologic 'planar cellular APC model' for improved imaging and interrogation of fundamental antigenic signaling processes will be described. Video LinkThe video component of this article can be found at

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“…The increased Ca 2+ levels then activate the protein phosphatase calcineurin (Klee et al, 1979) by disrupting the inhibitory effects of calmodulin. Calcineurin activation leads to the dephosphorylation of NFAT, allowing it to enter the nucleus, where it co-operates with other transcription factors to bind promoters (Burbach et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Surface CD3 expression proceeds through both myosin regulatory light chain 9 (MYL9)-dependent and MYL9-independent pathways in Jurkat cells

Aoki

Miyazaki

Katayama

et al. 2012

J. Smooth Muscle Res.

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CD3 is a complex of polypeptides which form part of the T cell receptor. Normal human peripheral pan T cells, express not only CD3, but the mRNA for myosin regulatory light chains MYL9, MYL12A, and MYL12B are also significantly expressed. In the Jurkat wild strain, an acute T cell leukemia cell line, CD3 on the surface and MYL9 mRNA are not expressed, while both MYL12A mRNA and MYL12B mRNA are expressed. Jurkat-I, a new clone was established by the transfection of the MYL9 gene into the Jurkat wild strain. As a result, the level of CD3 expressed on the surface of Jurkat-I cells was significantly higher than those in the Jurkat wild strain. Phorbol 12-myristate 13-acetate increased the surface CD3 levels in Jurkat wild strain cells without resulting in MYL9 gene expression, indicating that protein kinase C is partially involved in the expression of CD3 on the surface. These results suggest that surface CD3 expression proceeds through both MYL9-dependent and MYL9-independent pathways (i.e. the protein kinase C-dependent pathway) in Jurkat cells.

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T‐cell receptor signaling to integrins

Cited by 130 publications

References 163 publications

Tetraspanins CD9 and CD151 at the immune synapse support T‐cell integrin signaling

Tetraspanins CD9 and CD151 at the immune synapse support T‐cell integrin signaling

An Endothelial Planar Cell Model for Imaging Immunological Synapse Dynamics

Surface CD3 expression proceeds through both myosin regulatory light chain 9 (MYL9)-dependent and MYL9-independent pathways in Jurkat cells

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