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Requirements for peptide-induced T cell receptor downregulation on naive CD8+ T cells.

Cai Z, Kishimoto H, Brunmark A, Jackson MR, Peterson PA, Sprent J - J. Exp. Med. (1997)

Bottom Line: These stringent requirements did not apply to TCR downregulation.Thus, TCR downregulation seemed to depend solely on TCR/peptide/interaction and did not require either CD8 or B7-1 expression; ICAM-1 potentiated TCR downregulation, but only with limiting doses of peptides.TCR downregulation was most prominent with high affinity peptides and appeared to be neither obligatory nor sufficient for T cell activation.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, IMM4, The Scripps Research Institute, La Jolla, California 92037, USA.

ABSTRACT
The requirements for inducing downregulation of alpha/beta T cell receptor (TCR) molecules on naive major histocompatibility complex class I-restricted T cells was investigated with 2C TCR transgenic mice and defined peptides as antigen. Confirming previous results, activation of 2C T cells in response to specific peptides required CD8 expression on the responder cells and was heavily dependent upon costimulation provided by either B7-1 or ICAM-1 on antigen-presenting cells (APC). These stringent requirements did not apply to TCR downregulation. Thus, TCR downregulation seemed to depend solely on TCR/peptide/interaction and did not require either CD8 or B7-1 expression; ICAM-1 potentiated TCR downregulation, but only with limiting doses of peptides. TCR downregulation was most prominent with high affinity peptides and appeared to be neither obligatory nor sufficient for T cell activation. In marked contrast to T cell activation, TCR downregulation was resistant to various metabolic inhibitors. The biological significance of TCR downregulation is unclear, but could be a device for protecting T cells against excessive signaling.

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Influence of costimulation on TCR downregulation and T cell  activation. Purified CD8+ 2C cells (5 × 105) were incubated with the indicated transfected Drosophila cells (1 × 106) plus p2Ca or QL9 peptides  (10 μM) in bulk (2 ml) culture for 12 h and stained for TCR (1B2) and  CD8 expression. (Top) staining of noncultured 2C cells is shown as a control. The summarized data on proliferative responses of 2C cells to p2Ca  and QL9 peptides are taken from Cai et al. (21).
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Figure 4: Influence of costimulation on TCR downregulation and T cell activation. Purified CD8+ 2C cells (5 × 105) were incubated with the indicated transfected Drosophila cells (1 × 106) plus p2Ca or QL9 peptides (10 μM) in bulk (2 ml) culture for 12 h and stained for TCR (1B2) and CD8 expression. (Top) staining of noncultured 2C cells is shown as a control. The summarized data on proliferative responses of 2C cells to p2Ca and QL9 peptides are taken from Cai et al. (21).

Mentions: In initial experiments, 2C T cells were cultured with B10.D2 spleen cells plus QL9 peptide (10−5 M) in the presence of CTLA4Ig, a reagent that binds to B7-1 and B7-2 on APCs and thus blocks CD28/B7 interaction (39). Even at high concentrations, CTLA4Ig had little if any capacity to prevent TCR downregulation (data not shown). Since spleen APCs express a spectrum of molecules with potential costimulatory function, the role of individual costimulatory molecules on TCR downregulation was examined with the aid of a panel of Ld-transfected Drosophila cells as APCs. These cells expressed Ld alone (Ld APCs), Ld + B7-1 (Ld.B7), Ld + ICAM-1 (Ld.ICAM), or Ld + B7-1 + ICAM-1 (Ld.B7.ICAM). The capacity of these Drosophila APCs to elicit proliferative responses of 2C CD8+ cells in the absence of added cytokines is discussed elsewhere (21) and is summarized in Fig. 4, right. For QL9 peptide, proliferative responses are undetectable with Ld APCs, weak but detectable with Ld.B7 or Ld.ICAM APCs, and very strong with Ld.B7.ICAM APCs; for p2Ca peptides, proliferative responses are seen only with Ld.B7.ICAM APCs.


Requirements for peptide-induced T cell receptor downregulation on naive CD8+ T cells.

Cai Z, Kishimoto H, Brunmark A, Jackson MR, Peterson PA, Sprent J - J. Exp. Med. (1997)

Influence of costimulation on TCR downregulation and T cell  activation. Purified CD8+ 2C cells (5 × 105) were incubated with the indicated transfected Drosophila cells (1 × 106) plus p2Ca or QL9 peptides  (10 μM) in bulk (2 ml) culture for 12 h and stained for TCR (1B2) and  CD8 expression. (Top) staining of noncultured 2C cells is shown as a control. The summarized data on proliferative responses of 2C cells to p2Ca  and QL9 peptides are taken from Cai et al. (21).
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Related In: Results  -  Collection

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Figure 4: Influence of costimulation on TCR downregulation and T cell activation. Purified CD8+ 2C cells (5 × 105) were incubated with the indicated transfected Drosophila cells (1 × 106) plus p2Ca or QL9 peptides (10 μM) in bulk (2 ml) culture for 12 h and stained for TCR (1B2) and CD8 expression. (Top) staining of noncultured 2C cells is shown as a control. The summarized data on proliferative responses of 2C cells to p2Ca and QL9 peptides are taken from Cai et al. (21).
Mentions: In initial experiments, 2C T cells were cultured with B10.D2 spleen cells plus QL9 peptide (10−5 M) in the presence of CTLA4Ig, a reagent that binds to B7-1 and B7-2 on APCs and thus blocks CD28/B7 interaction (39). Even at high concentrations, CTLA4Ig had little if any capacity to prevent TCR downregulation (data not shown). Since spleen APCs express a spectrum of molecules with potential costimulatory function, the role of individual costimulatory molecules on TCR downregulation was examined with the aid of a panel of Ld-transfected Drosophila cells as APCs. These cells expressed Ld alone (Ld APCs), Ld + B7-1 (Ld.B7), Ld + ICAM-1 (Ld.ICAM), or Ld + B7-1 + ICAM-1 (Ld.B7.ICAM). The capacity of these Drosophila APCs to elicit proliferative responses of 2C CD8+ cells in the absence of added cytokines is discussed elsewhere (21) and is summarized in Fig. 4, right. For QL9 peptide, proliferative responses are undetectable with Ld APCs, weak but detectable with Ld.B7 or Ld.ICAM APCs, and very strong with Ld.B7.ICAM APCs; for p2Ca peptides, proliferative responses are seen only with Ld.B7.ICAM APCs.

Bottom Line: These stringent requirements did not apply to TCR downregulation.Thus, TCR downregulation seemed to depend solely on TCR/peptide/interaction and did not require either CD8 or B7-1 expression; ICAM-1 potentiated TCR downregulation, but only with limiting doses of peptides.TCR downregulation was most prominent with high affinity peptides and appeared to be neither obligatory nor sufficient for T cell activation.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, IMM4, The Scripps Research Institute, La Jolla, California 92037, USA.

ABSTRACT
The requirements for inducing downregulation of alpha/beta T cell receptor (TCR) molecules on naive major histocompatibility complex class I-restricted T cells was investigated with 2C TCR transgenic mice and defined peptides as antigen. Confirming previous results, activation of 2C T cells in response to specific peptides required CD8 expression on the responder cells and was heavily dependent upon costimulation provided by either B7-1 or ICAM-1 on antigen-presenting cells (APC). These stringent requirements did not apply to TCR downregulation. Thus, TCR downregulation seemed to depend solely on TCR/peptide/interaction and did not require either CD8 or B7-1 expression; ICAM-1 potentiated TCR downregulation, but only with limiting doses of peptides. TCR downregulation was most prominent with high affinity peptides and appeared to be neither obligatory nor sufficient for T cell activation. In marked contrast to T cell activation, TCR downregulation was resistant to various metabolic inhibitors. The biological significance of TCR downregulation is unclear, but could be a device for protecting T cells against excessive signaling.

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