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  • The American Association of Immunologists  (4)
  • Dietrich, Jes  (4)
  • Geisler, Carsten  (4)
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  • The American Association of Immunologists  (4)
Language
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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
    Library Location Call Number Volume/Issue/Year Availability
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  • 2
    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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  • 3
    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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  • 4
    Online Resource
    Online Resource
    The American Association of Immunologists ; 1998
    In:  The Journal of Immunology Vol. 161, No. 1 ( 1998-07-01), p. 260-267
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 161, No. 1 ( 1998-07-01), p. 260-267
    Abstract: TCR down-regulation plays an important role in modulating T cell responses both during T cell development and in mature T cells. Down-regulation of the TCR is induced by engagement of the TCR by specific ligands and/or by activation of protein kinase C (PKC). We report here that ligand- and PKC-induced TCR down-regulation is mediated by two distinct, independent mechanisms. Ligand-induced TCR down-regulation is dependent on the protein tyrosine kinases p56lck and p59fyn but independent of PKC and the CD3γ leucine-based (L-based) internalization motif. In contrast, PKC-induced TCR down-regulation is dependent on the CD3γ L-based internalization motif but independent of p56lck and p59fyn. Finally, our data indicate that in the absence of TCR ligation, TCR expression levels can be finely regulated via the CD3γ L-based motif by the balance between PKC and serine/threonine protein phosphatase activities. Such a TCR ligation-independent regulation of TCR expression levels could probably be important in determining the activation threshold of T cells in their encounter with APC.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    RVK:
    RVK:
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 1998
    detail.hit.zdb_id: 1475085-5
    Library Location Call Number Volume/Issue/Year Availability
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