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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 B7-1  and ICAM-1 expression on peptide-induced 2C TCR downregulation. (A) 5 × 105 purified  CD8+ 2C cells were cultured  with 1 × 106 Drosophila APCs in  the presence of a titrated concentration of QL9 peptides for  12 h. The cells were harvested  and stained with FITC-conjugated 1B2 or FITC-conjugated  anti-CD69. The data show TCR  and CD69 expression on gated  CD8+ 2C cells. The data in A  and B are from two separate experiments.
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Figure 5: Influence of B7-1 and ICAM-1 expression on peptide-induced 2C TCR downregulation. (A) 5 × 105 purified CD8+ 2C cells were cultured with 1 × 106 Drosophila APCs in the presence of a titrated concentration of QL9 peptides for 12 h. The cells were harvested and stained with FITC-conjugated 1B2 or FITC-conjugated anti-CD69. The data show TCR and CD69 expression on gated CD8+ 2C cells. The data in A and B are from two separate experiments.

Mentions: The above data apply to high concentrations of peptides (10−5 M). The effects of using limiting doses of QL9 peptide are shown in Fig. 5. Under these conditions, the capacity of Ld and Ld.B7 APCs to cause QL9-mediated TCR downregulation of naive 2C cells was virtually identical, implying that B7-1 expression played no detectable role in TCR downregulation. Interestingly, in contrast to B7-1, ICAM-1 expression appeared to potentiate TCR downregulation. Thus, at limiting doses of peptides (10−7–10−9 M) TCR downregulation was more pronounced with ICAM-1+ APCs (Ld.ICAM or Ld.B7.ICAM cells) than with ICAM-1− APCs (Ld or Ld.B7 APCs; Fig. 5 A, left). Several other experiments, e.g., Fig. 5 B, gave similar results.


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 B7-1  and ICAM-1 expression on peptide-induced 2C TCR downregulation. (A) 5 × 105 purified  CD8+ 2C cells were cultured  with 1 × 106 Drosophila APCs in  the presence of a titrated concentration of QL9 peptides for  12 h. The cells were harvested  and stained with FITC-conjugated 1B2 or FITC-conjugated  anti-CD69. The data show TCR  and CD69 expression on gated  CD8+ 2C cells. The data in A  and B are from two separate experiments.
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Related In: Results  -  Collection

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Figure 5: Influence of B7-1 and ICAM-1 expression on peptide-induced 2C TCR downregulation. (A) 5 × 105 purified CD8+ 2C cells were cultured with 1 × 106 Drosophila APCs in the presence of a titrated concentration of QL9 peptides for 12 h. The cells were harvested and stained with FITC-conjugated 1B2 or FITC-conjugated anti-CD69. The data show TCR and CD69 expression on gated CD8+ 2C cells. The data in A and B are from two separate experiments.
Mentions: The above data apply to high concentrations of peptides (10−5 M). The effects of using limiting doses of QL9 peptide are shown in Fig. 5. Under these conditions, the capacity of Ld and Ld.B7 APCs to cause QL9-mediated TCR downregulation of naive 2C cells was virtually identical, implying that B7-1 expression played no detectable role in TCR downregulation. Interestingly, in contrast to B7-1, ICAM-1 expression appeared to potentiate TCR downregulation. Thus, at limiting doses of peptides (10−7–10−9 M) TCR downregulation was more pronounced with ICAM-1+ APCs (Ld.ICAM or Ld.B7.ICAM cells) than with ICAM-1− APCs (Ld or Ld.B7 APCs; Fig. 5 A, left). Several other experiments, e.g., Fig. 5 B, gave similar results.

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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