T cell receptor α‐chain tail is required for protein kinase C‐mediated down‐regulation, but not for signaling

Bt, Bäckström; Rubin, Bent; Peter, Annick; Tiefenthaler, Georg; Palmer, Ed

doi:10.1002/eji.1830270621

Cited by 21 publications

(9 citation statements)

References 69 publications

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“…The discrepancy between our findings and the data of Bäckström et al [16] and Viola et al [17] is partially resolved by the effects of brefeldin A (BFA) ( Fig. 5E-H).…”

Section: Discussioncontrasting

confidence: 96%

“…Here, we determined TCR together with CD8 expression in response to full or partial agonists. A comodulation of TCR and CD4 in mouse T cell hybridomas has been reported by Bäckström et al [16] and CD4 as well as CD8 were described to be co-modulated with TCR on human T cell clones [17].…”

Section: Effects Of Receptor Activation On Tcr and Cd8 Expressionmentioning

confidence: 62%

“…Another phenomenon which has recently been described for mouse T cell hybridomas [16] and human T cell clones [17] is the stoichiometric co-modulation of CD4 or CD8 coreceptors with TCR in response to antigenic stimuli. For CD8 + mouse T cell clones we demonstrate that only one of three clones shows synchronized down-regulation of TCR and CD8, and this only in response to the inducing full agonist ( Fig.…”

Section: Discussionmentioning

confidence: 94%

“…In most, but not all (see clone D1), cases the export of CD8 exceeds the rate of internalization, resulting in a net increase of surface expression. Whether this difference in the behavior of clone D1 or clones described by others [16,17] results from particular TCR properties remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

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Partial agonism and independent modulation of T cell receptor and CD8 in hapten-specific cytotoxic T cells

et al. 1998

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We recently demonstrated antagonism for hapten-reactive T cells by altered hapten ligands. Here we investigated partial peptide-or hapten-agonism and effects of antigen stimulation on the expression of TCR and the CD8 coreceptor using a set of DNP-or TNP-peptide-induced, H-2K b-restricted mouse CTL clones. Various K b-binding TNP-and DNP-peptides acted as partial agonists, cross-reactively stimulating individual clones for cytotoxicity and IFN-+ secretion, but failing to induce proliferation or TNF-§ production. Full agonism, i.e. activation of all possible functions, was usually restricted to those hapten-peptide combinations used for the induction of the respective clones. Our data imply distinctive kinetic optima for TCR antigen contacts in the induction of the various T cell effector functions. Down-regulation of TCR was efficiently induced by full, but with one exception not by partial, agonists, indicating the independence of cytotoxicity or IFN-+ secretion from TCR modulation. On the other hand, a reduction of TCR expression induced by full agonists was usually not accompanied by synchronous down-modulation of CD8 as reported by others for human T cells. In fact, three of four full agonists and all partial agonists markedly enhanced rather than reduced the expression of CD8. Increased CD8 surface levels enhanced cytolytic potential and increased cross-reactivity patterns of individual clones. Brefeldin A blocked this CD8 induction by partial agonists, and in the case of full agonists resulted in a parallel reduction of both, TCR and CD8. Thus, antigenic stimulation of mouse T cells initially down-modulates CD8 together with TCR, but the loss of coreceptor is over-compensated by a signal for increased CD8 export.

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“…The discrepancy between our findings and the data of Bäckström et al [16] and Viola et al [17] is partially resolved by the effects of brefeldin A (BFA) ( Fig. 5E-H).…”

Section: Discussioncontrasting

confidence: 96%

Section: Effects Of Receptor Activation On Tcr and Cd8 Expressionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Partial agonism and independent modulation of T cell receptor and CD8 in hapten-specific cytotoxic T cells

et al. 1998

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“…Thus, although they involve different mechanisms [30,46], our data show that ligand-or PMA-induced TCR downregulation result in similar alterations of P14 CTL reactivity (Figs. 5, 6).…”

Section: Discussionmentioning

confidence: 50%

Transient alteration of T cell fine specificity by a strong primary stimulus correlates with T cell receptor down-regulation

Martin

Bevan

1998

Eur. J. Immunol.

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P14 mice expressing a transgenic TCR specific for the lymphocytic choriomeningitis virus glycoprotein p33 epitope were used to study the induction of CTL effector activity by a variety of ligands. Surprisingly, p33 variants which are weaker agonists for the P14 TCR than the wild-type p33 peptide were able to induce more potent effectors with a broader range of cytolytic specificity. Similarly, low concentrations of p33 were more effective than higher concentrations. These results correlated with no or only moderate TCR down-regulation by variants of p33 and low p33 concentrations. This phenotype observed after 18 h of culture was transient as progressive restoration of reactivity was observed at 42 or 66 h in the cultures stimulated with high p33 concentrations and this correlated with recovery of TCR surface levels. TCR down-regulation was blocked by src family kinase inhibitors. These findings indicate that the specificity of a T cell can be fine-tuned by the nature of the primary stimulus correlating with surface TCR level and imply an important role for src family kinases in the differential regulation of surface TCR levels upon TCR engagement by different ligand/MHC complexes.

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Transient alteration of T cell fine specificity by a strong primary stimulus correlates with T cell receptor down-regulation

Martin

Bevan

1998

Eur. J. Immunol.

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T cell receptor α‐chain tail is required for protein kinase C‐mediated down‐regulation, but not for signaling

Cited by 21 publications

References 69 publications

Partial agonism and independent modulation of T cell receptor and CD8 in hapten-specific cytotoxic T cells

Partial agonism and independent modulation of T cell receptor and CD8 in hapten-specific cytotoxic T cells

Transient alteration of T cell fine specificity by a strong primary stimulus correlates with T cell receptor down-regulation

Transient alteration of T cell fine specificity by a strong primary stimulus correlates with T cell receptor down-regulation

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