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  • The American Association of Immunologists  (6)
  • Dietrich, Jes  (6)
  • 2000-2004  (6)
Type of Medium
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  • The American Association of Immunologists  (6)
Language
Years
  • 2000-2004  (6)
Year
Subjects(RVK)
  • 1
    Online Resource
    Online Resource
    The American Association of Immunologists ; 2000
    In:  The Journal of Immunology Vol. 165, No. 6 ( 2000-09-15), p. 3065-3072
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 165, No. 6 ( 2000-09-15), p. 3065-3072
    Abstract: The TCR is a constitutively recycling receptor meaning that a constant fraction of TCR from the plasma membrane is transported inside the cell at the same time as a constant fraction of TCR from the intracellular pool is transported to the plasma membrane. TCR recycling is affected by protein kinase C activity. Thus, an increase in protein kinase C activity affects TCR recycling kinetics leading to a new TCR equilibrium with a reduced level of TCR expressed at the T cell surface. Down-regulation of TCR expression compromises T cell activation. Conversely, TCR up-regulation is expected to increase T cell responsiveness. The purpose of this study was to identify and characterize potential pathways for TCR up-regulation. We found that ceramide affected TCR recycling dynamics and induced TCR up-regulation in a concentration- and time-dependent manner. Experiments applying phosphatase inhibitors indicated that ceramide-induced TCR up-regulation was most probably mediated by serine/threonine protein phosphatase 2A. Analyses of T cell variants demonstrated that TCR up-regulation was dependent on the presence of an intact CD3γ L-based motif and thus acted on TCR engaged in the recycling pathway. Finally, we showed that TCR up-regulation probably plays a physiological role by increasing T cell responsiveness. Thus, by affecting the TCR recycling kinetics, T cells have the potential both to up- and down-regulate TCR expression and thereby adjust T cell responsiveness.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    RVK:
    RVK:
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2000
    detail.hit.zdb_id: 1475085-5
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  • 2
    Online Resource
    Online Resource
    The American Association of Immunologists ; 2001
    In:  The Journal of Immunology Vol. 166, No. 4 ( 2001-02-15), p. 2514-2521
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 166, No. 4 ( 2001-02-15), p. 2514-2521
    Abstract: Ig-like transcript 2 (ILT2)/leukocyte Ig-like receptor 1 (LIR1) is a receptor, specific for MHC class I molecules, that inhibits lymphoid and myeloid cells. Here, we analyzed the molecular and cellular mechanisms by which ILT2 modulates T cell activation in primary CTLs and transfected T cell lines. We found that cross-linking with the TCR and the activity of Src tyrosine kinase p56lck were required for phosphorylation of ILT2 and subsequent recruitment of Src homology protein 1. In contrast, ILT2 triggering resulted in reduced phosphorylation of TCRζ and linker for activation of T cells, which led to reduced TCRζ-ZAP70 complex formation, as well as extracellular signal-related kinase 1 and 2 activation. Furthermore, ILT2 inhibited both superantigen and anti-TCR Ab-induced rearrangement of the actin cytoskeleton. The inhibitory effect mediated by ILT2 is probably concentrated at the APC-T cell interface because both TCR and ILT2 were strongly polarized toward the APC upon engagement by their specific ligands. Thus, ILT2 inhibits both signaling and cellular events involved in the activation of T cells.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    RVK:
    RVK:
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2001
    detail.hit.zdb_id: 1475085-5
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  • 3
    Online Resource
    Online Resource
    The American Association of Immunologists ; 2000
    In:  The Journal of Immunology Vol. 164, No. 10 ( 2000-05-15), p. 4991-4995
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 164, No. 10 ( 2000-05-15), p. 4991-4995
    Abstract: We have identified new activating receptors of the Ig superfamily expressed on human myeloid cells, called TREM (triggering receptor expressed on myeloid cells). TREM-1 is selectively expressed on blood neutrophils and a subset of monocytes and is up-regulated by bacterial LPS. Engagement of TREM-1 triggers secretion of IL-8, monocyte chemotactic protein-1, and TNF-α and induces neutrophil degranulation. Intracellularly, TREM-1 induces Ca2+ mobilization and tyrosine phosphorylation of extracellular signal-related kinase 1 (ERK1), ERK2 and phospholipase C-γ. To mediate activation, TREM-1 associates with the transmembrane adapter molecule DAP12. Thus, TREM-1 mediates activation of neutrophil and monocytes, and may have a predominant role in inflammatory responses.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    RVK:
    RVK:
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2000
    detail.hit.zdb_id: 1475085-5
    Library Location Call Number Volume/Issue/Year Availability
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  • 4
    Online Resource
    Online Resource
    The American Association of Immunologists ; 2002
    In:  The Journal of Immunology Vol. 168, No. 11 ( 2002-06-01), p. 5434-5440
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 168, No. 11 ( 2002-06-01), p. 5434-5440
    Abstract: TCR internalization takes place both in resting T cells as part of constitutive TCR cycling, after PKC activation, and during TCR triggering. It is still a matter of debate whether these pathways represent distinct pathways. Thus, some studies have indicated that ligand-induced TCR internalization is regulated by mechanisms distinct from those involved in constitutive internalization, whereas other studies have suggested that the ligand-induced TCR internalization pathway is identical with the constitutive pathway. To resolve this question, we first identified requirements for constitutive TCR cycling. We found that in contrast to PKC-induced TCR internalization where both CD3γ-S126 and the CD3γ leucine-based internalization motif are required, constitutive TCR cycling required neither PKC nor CD3γ-S126 but only the CD3γ leucine-based motif. Having identified these requirements, we next studied ligand-induced internalization in cells with abolished constitutive TCR cycling. We found that ligand-induced TCR internalization was not dependent on constitutive TCR internalization. Likewise, constitutive internalization and recycling of the TCR were independent of an intact ligand-induced internalization of the TCR. In conclusion, ligand-induced TCR internalization and constitutive cycling of the TCR represents two independent pathways regulated by different mechanisms.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    RVK:
    RVK:
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2002
    detail.hit.zdb_id: 1475085-5
    Library Location Call Number Volume/Issue/Year Availability
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  • 5
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 168, No. 9 ( 2002-05-01), p. 4519-4523
    Abstract: TCR down-regulation plays an important role in modulating T cell responses both during T cell development and in mature T cells. At least two distinct pathways exist for down-regulation of the TCR. One pathway is activated following TCR ligation and is dependent on tyrosine phosphorylation. The other pathway is dependent on protein kinase C (PKC)-mediated activation of the CD3γ di-leucine-based receptor-sorting motif. Previous studies have failed to demonstrate a connection between ligand- and PKC-induced TCR down-regulation. Thus, although an apparent paradox, the dogma has been that ligand- and PKC-induced TCR down-regulations are not interrelated. By analyses of a newly developed CD3γ-negative T cell variant, freshly isolated and PHA-activated PBMC, and a mouse T cell line, we challenged this dogma and demonstrate in this work that PKC activation and the CD3γ di-leucine-based motif are indeed required for efficient ligand-induced TCR down-regulation.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    RVK:
    RVK:
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2002
    detail.hit.zdb_id: 1475085-5
    Library Location Call Number Volume/Issue/Year Availability
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  • 6
    Online Resource
    Online Resource
    The American Association of Immunologists ; 2000
    In:  The Journal of Immunology Vol. 164, No. 1 ( 2000-01-01), p. 9-12
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 164, No. 1 ( 2000-01-01), p. 9-12
    Abstract: Signal-regulatory proteins (SIRPs) are cell-surface glycoproteins expressed on myeloid and neural cells that have been shown to recruit SH2 domain-containing protein phosphatase 1 (SHP-1) and SHP-2 and to regulate receptor tyrosine kinase-coupled signaling. One SIRP of unknown function, designated SIRPβ1, contains a short cytoplasmic domain that lacks sequence motifs capable of recruiting SHP-1 and SHP-2. Using a SIRP-specific mAb, we show that SIRPβ1 is expressed in monocytes and dendritic cells and associates with the signal transduction molecule DAP12. SIRPβ1/DAP12 complex formation was required for efficient cell-surface expression of SIRPβ1. Stimulation of this complex induced tyrosine phosphorylation, mitogen-activated protein kinase activation, and cellular activation. Thus, SIRPβ1 is a new DAP12-associated receptor involved in the activation of myeloid cells.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    RVK:
    RVK:
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2000
    detail.hit.zdb_id: 1475085-5
    Library Location Call Number Volume/Issue/Year Availability
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