Dendritic Cells Sensitize TCRs through Self-MHC-Mediated Src Family Kinase Activation

Meraner, Paul; Hořejšı́, Václav; Wölpl, A; Fischer, Gottfried; Stingl, Georg; Maurer, Dieter

doi:10.4049/jimmunol.178.4.2262

Cited by 3 publications

(4 citation statements)

References 56 publications

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“…One recent study identified a T cell activation during adhesion to immature dendritic cells in the absence of cognate Ag and attributed this to presentation of self-Ag (37). However, our findings show that the T cell raft capping by unpulsed B cell APCs occurs independently of MHC II, and thus is unlikely to depend on presentation of self-Ag.…”

Section: Discussioncontrasting

confidence: 56%

Early and Dynamic Polarization of T Cell Membrane Rafts and Constituents Prior to TCR Stop Signals

Komen

Mishra

Byrum

et al. 2007

The Journal of Immunology

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Polarization of membrane rafts and signaling proteins to form an immunological synapse is a hallmark of T cell stimulation. However, the kinetics of raft polarization and associated proteins in relation to the initial contact of the T cell with the APC are poorly defined. We addressed this question by measuring the distribution of membrane-targeted fluorescent protein markers during initial T cell interactions with B cell APCs. Experiments with unpulsed B cells lacking cognate Ag demonstrated an MHC class II-independent capping that was specific to membrane raft markers and required actin rearrangements and signals from Src kinases and PI3K. By live cell imaging experiments, we identified a similar specific polarization of membrane raft markers before TCR-dependent stop signals, and which occurred independently of cognate peptide-MHC class II. T cells conjugated to unpulsed B cells exhibited capping of CD4 and microclusters of the TCR ζ-chain, but only the CD4 enrichment was cholesterol dependent. Furthermore, raft association of CD4 was necessary for its efficient targeting to the Ag-independent caps. Interestingly, anergic Vβ8+ T cells isolated from staphylococcal enterotoxin B-injected mice did not exhibit Ag-independent capping of membrane rafts, showing that inhibition of these early, Ag-independent events is a property associated with tolerance. Altogether, these data show that membrane raft capping is one of the earliest events in T cell activation and represents one avenue for promoting and regulating downstream peptide-MHC-dependent signaling within the T cell.

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Section: Discussioncontrasting

confidence: 56%

Early and Dynamic Polarization of T Cell Membrane Rafts and Constituents Prior to TCR Stop Signals

Komen

Mishra

Byrum

et al. 2007

The Journal of Immunology

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“…11 In the current study, we observed that the same BMDCs captured both CT and PE (data not shown), indicating that these DCs have an opportunity to process these 2 molecules simultaneously to produce mediators to direct subsequent immune reactions. We also observed that CT upregulated costimulatory molecules CD80 and CD86, and MHC II on DCs, in agreement with previous reports.…”

Section: Discussionmentioning

confidence: 53%

“…DCs capture and process exogenous antigens and transfer the antigenic information to T cells. 11 DCs also produce costimulatory molecules to assist the process of antigen information transfer and T-cell activation. 12 Subsequently, the naive CD4 1 T cells develop to T H 1 or T H 2 cells according to the cytokine milieu.…”

mentioning

confidence: 99%

Disruption of T-cell immunoglobulin and mucin domain molecule (TIM)–1/TIM4 interaction as a therapeutic strategy in a dendritic cell–induced peanut allergy model

Feng¹,

Chen²,

He³

et al. 2008

Journal of Allergy and Clinical Immunology

101

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“…The underlying signals provided by DC despite the absence of high-affinity peptides include MHC-class II-dependent and -independent signals, including Ca 11 -influx and the tyrosine phosphorylation (pY) of z-chain and Src kinases [21][22][23] and, likely, cytokine-derived signals [14].…”

Section: Introductionmentioning

confidence: 99%

A dynamic immunological synapse mediates homeostatic TCR‐dependent and ‐independent signaling

2010

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For homeostasis, T cells integrate non-cognate TCR-dependent and -independent signals to survive and weakly proliferate. In contrast to antigen-specific, stable, and long-lived contacts, signaling in short-lived homeostatic interactions depends upon the coordination of ongoing T-cell migration on the surface of DC and signaling at the cell-cell junction.To mimic peripheral tissues and analyze how T-cell migration and cell-cell signaling are integrated, we used live-cell imaging and 3-D reconstruction of fixed conjugates between DO11.10 T cells and DC in 3-D low-density collagen matrices. T cells simultaneously maintained amoeboid migration and polarized towards the DC, leading to a fully dynamic interaction plane that delivered signals for homeostatic T-cell survival and proliferation. The contact plane comprised three zones, the actin-rich leading edge poor in signal but driving migration, a mid-zone mediating TCR/MHC-induced signal associated with proliferation, and the rear uropod mediating predominantly MHC-independent signals. Thus a dynamic immunological synapse with distinct signaling sectors enables moving T cells to serially sample resident tissue cells and acquire molecular information ''en passant''.Key words: Immunological synpase . Migration . T-cell homeostasis Supporting Information available online IntroductionLymphocyte recirculation and amoeboid migration within secondary lymphoid tissues are mandatory for effective immune surveillance. In secondary lymphoid organs, T cells utilize amoeboid migration along fibroblastic reticular cells as guidance cues to rapidly scan APC for cognate antigen [1,2]. Whereas the role of migration in scanning cells for their antigenic repertoire is well established, its role in T-cell activation and signal induction is less clear. On the one hand, in vitro models suggest that the recognition of antigenic peptide leads to migratory arrest [3] and the formation of a concentrically segregated interaction plane with a peripheral ring of adhesion molecules surrounding a central accumulation of TCR, the immunological synapse (IS) [4,5]. Conversely, the most powerful APC, DC, activate T cells via both stably adhesive and migratory contacts, depending on signal strength and phase of T-cell priming [6][7][8][9] and do not induce a segregated IS [10,11]. In a lipid bilayer model, the concept of productive TCR signaling despite T-cell migration is suggested by intermittent episodes of T-cell migration, which are associated with enhanced TCR signaling and IL-2 secretion [12]. Thus, the spectrum of activating T-cell/APC interactions is diverse and T-cell migration appears to contribute to rather than interfere with signal induction. However, as adhesive and migratory contact phases alternate sequentially in most experimental models, the specific topography and function of migratory phases remain unclear.In contrast to antigen-specific contacts, in vivo interactions between T cells and DC that do not present cognate antigen are Due to their intrinsic dynamics coupled to signal i...

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Dendritic Cells Sensitize TCRs through Self-MHC-Mediated Src Family Kinase Activation

Cited by 3 publications

References 56 publications

Early and Dynamic Polarization of T Cell Membrane Rafts and Constituents Prior to TCR Stop Signals

Early and Dynamic Polarization of T Cell Membrane Rafts and Constituents Prior to TCR Stop Signals

Disruption of T-cell immunoglobulin and mucin domain molecule (TIM)–1/TIM4 interaction as a therapeutic strategy in a dendritic cell–induced peanut allergy model

A dynamic immunological synapse mediates homeostatic TCR‐dependent and ‐independent signaling

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