Modulation of immunological synapse by membrane-bound and soluble ligands

González, Pablo A.; Carreño, Leandro J.; Figueroa, Claudio; Kalergis, Alexis M.

doi:10.1016/j.cytogfr.2007.01.003

Cited by 38 publications

(56 citation statements)

References 160 publications

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“…Because of its importance, several viruses have evolved molecular mechanisms to impair T-cell activation and gain advantage over the host immune response to disseminate within infected tissues. 33,38 Given that DCs play a major role in naive T-cell priming, several pathogens have evolved molecular mechanisms to impair the function of DCs. 10,31,39 A recent study using antigen-specific mouse T cells showed that conventional DCs isolated from hMPVinfected lungs fail to induce the proliferation of pOVAspecific DO11.10 T cells.…”

Section: Discussionmentioning

confidence: 99%

“…31 Because T cells polarize their Golgi apparatus towards DCs during IS formation, we assessed this process as a readout for IS assembly. [31][32][33] As shown in Fig. 4, hMPV failed to suppress the capacity of DCs to induce T-cell polarization in response to antigenic stimulation when compared with mock or UV-hMPV-inoculated DCs (Fig.…”

Section: Hmpv Does Not Interfere With Dc-t-cell Synapse Assemblymentioning

confidence: 99%

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Human metapneumovirus keeps dendritic cells from priming antigen‐specific naive T cells

2013

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SummaryHuman metapneumovirus (hMPV) is the second most common cause of acute lower respiratory tract infections in children, causing a significant public health burden worldwide. Given that hMPV can repeatedly infect the host without major antigenic changes, it has been suggested that hMPV may have evolved molecular mechanisms to impair host adaptive immunity and, more specifically, T-cell memory. Recent studies have shown that hMPV can interfere with superantigen-induced T-cell activation by infecting conventional dendritic cells (DCs). Here, we show that hMPV infects mouse DCs in a restricted manner and induces moderate maturation. Nonetheless, hMPV-infected DCs are rendered inefficient at activating naive antigen-specific CD4 + T cells (OT-II), which not only display reduced proliferation, but also show a marked reduction in surface activation markers and interleukin-2 secretion. Decreased T-cell activation was not mediated by interference with DC-T-cell immunological synapse formation as recently described for the human respiratory syncytial virus (hRSV), but rather by soluble factors secreted by hMPV-infected DCs. These data suggest that although hMPV infection is restricted within DCs, it is sufficient to interfere with their capacity to activate naive T cells. Altogether, by interfering with DC function and productive priming of antigen-inexperienced T cells, hMPV could impair the generation of long-term immunity.

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Section: Discussionmentioning

confidence: 99%

Section: Hmpv Does Not Interfere With Dc-t-cell Synapse Assemblymentioning

confidence: 99%

Human metapneumovirus keeps dendritic cells from priming antigen‐specific naive T cells

2013

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“…At this specialized area of physical contact between T cells and APCs, adhesion molecules and TCRs are actively segregated into distinct supramolecular complexes (5). Signaling through both TCR and adhesion molecules at the synapse contribute to increasing intracellular concentration of calcium required for T cell activation (6).…”

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confidence: 99%

Gap Junctions at the Dendritic Cell-T Cell Interface Are Key Elements for Antigen-Dependent T Cell Activation

Elgueta

Tobar

Shoji

et al. 2009

The Journal of Immunology

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The acquired immune response begins with Ag presentation by dendritic cells (DCs) to naive T cells in a heterocellular cell-cell contact-dependent process. Although both DCs and T cells are known to express connexin43, a gap junction protein subunit, the role of connexin43 on the initiation of T cell responses remains to be elucidated. In the present work, we report the formation of gap junctions between DCs and T cells and their role on T cell activation during Ag presentation by DCs. In cocultures of DCs and T cells, Lucifer yellow microinjected into DCs is transferred to adjacent transgenic CD4+ T cells, only if the specific antigenic peptide was present at least during the first 24 h of cocultures. This dye transfer was sensitive to gap junction blockers, such as oleamide, and small peptides containing the extracellular loop sequences of conexin. Furthermore, in this system, gap junction blockers drastically reduced T cell activation as reflected by lower proliferation, CD69 expression, and IL-2 secretion. This lower T cell activation produced by gap junction blockers was not due to a lower expression of CD80, CD86, CD40, and MHC-II on DCs. Furthermore, gap junction blocker did not affect polyclonal activation of T cell induced with anti-CD3 plus anti-CD28 Abs in the absence of DCs. These results strongly suggest that functional gap junctions assemble at the interface between DCs and T cells during Ag presentation and that they play an essential role in T cell activation.

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“…The TCR/pMHC interaction defines the specificity of T-cell activation based on the recognition of a particular pMHC complex on the APC surface by the TCR (1,2). This recognition leads to the formation of a specialized structure, known as an immunological synapse (IS), characterized by molecular rearrangements involving segregation of surface molecules, polarization of secretory machinery, and signaling components at the T-cell-APC contact interface (3)(4)(5).…”

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confidence: 99%

“…Thus, TCR/pMHC binding half-life must be short enough to ensure that a single pMHC molecule serially engages several TCR molecules (12,13,22). The simultaneous fulfillment of both kinetic proofreading and TCR serial engagement implies that an optimal TCR-pMHC half-life would be required for an efficient activation of T cells in response to low density cognate pMHC (3,6,7,10). Several independent studies using different experimental systems have provided evidence supporting this notion (6-10, 17, 22-25).…”

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confidence: 99%

T-cell antagonism by short half-life pMHC ligands can be mediated by an efficient trapping of T-cell polarization toward the APC

Carreño

Riquelme

González

et al. 2009

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

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T-cell activation results from productive T-cell receptor (TCR) engagement by a cognate peptide-MHC (pMHC) complex on the antigen presenting cell (APC) surface, a process leading to the polarization of the T-cell secretory machinery toward the APC interface. We have previously shown that the half-life of the TCR/ pMHC interaction and the density of pMHC on the APC are two parameters determining T-cell activation. However, whether the half-life of the TCR/pMHC interaction can modulate the efficiency of T-cell secretory machinery polarization toward an APC still remains unclear. Here, by using altered peptide ligands conferring different half-lives to the TCR/pMHC interaction, we have tested how this parameter can control T-cell polarization. We observed that only TCR/pMHC interactions with intermediate half-lives can promote the assembly of synapses that lead to T-cell activation. Strikingly, intermediate half-life interactions can be competed out by short half-life interactions, which can efficiently promote T-cell polarization and antagonize T-cell activation that was induced by activating intermediate half-life interactions. However, short TCR/ pMHC interactions fail at promoting phosphorylation of signaling molecules at the T-cell-APC contact interface, which are needed for T-cell activation. Our data suggest that although intermediate half-life pMHC ligands promote assembly of activating synapses, this process can be inhibited by short half-life antagonistic pMHC ligands, which promote the assembly of non activating synapses.immunological synapse | T-cell receptor | T-cell receptor half-life | dendritic cells

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Modulation of immunological synapse by membrane-bound and soluble ligands

Cited by 38 publications

References 160 publications

Human metapneumovirus keeps dendritic cells from priming antigen‐specific naive T cells

Human metapneumovirus keeps dendritic cells from priming antigen‐specific naive T cells

Gap Junctions at the Dendritic Cell-T Cell Interface Are Key Elements for Antigen-Dependent T Cell Activation

T-cell antagonism by short half-life pMHC ligands can be mediated by an efficient trapping of T-cell polarization toward the APC

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