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High-Affinity Ligands Can Trigger T Cell Receptor Signaling Without CD45 Segregation
Mohammad Ameen Al-Aghbar1,2,3, Yeh-Shiu Chu4, Bing-Mae Chen1
1Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Frontiers in Immunology
|April 25, 2018
Summary
T cell receptor (TCR) triggering is complex. CD45 phosphatase segregation from TCRs is not essential for initial T cell activation, challenging previous hypotheses.
Area of Science:
- Immunology
- Cell Signaling
- Biophysics
Background:
- T cell receptor (TCR) signaling initiation mechanisms remain unclear.
- A proposed model suggests CD45 phosphatase segregation from engaged TCRs is crucial for initiating signaling.
- This segregation is thought to favor ITAM phosphorylation in CD3 molecules.
Purpose of the Study:
- To investigate the role of CD45 segregation in TCR triggering.
- To determine if CD45 segregation is mandatory for initiating TCR signaling.
- To examine the influence of ligand affinity and length on CD45 segregation and T cell activation.
Main Methods:
- Utilized total internal reflection microscopy to observe CD45 segregation from TCRs.
- Employed anti-CD3 scFv with varying affinities (high/low) and molecular lengths.
- Studied Jurkat T cells stimulated on supported lipid bilayers.
Main Results:
- High-affinity ligands, regardless of length, induced T cell activation (calcium mobilization, Zap70 phosphorylation, cytokine secretion).
- CD45 segregated less from TCR microclusters with elongated ligands compared to short ones.
- Early T cell activation markers did not correlate with CD45 segregation, especially with elongated high-affinity ligands.
Conclusions:
- CD45 segregation from engaged TCRs is not mandatory for the initial triggering of TCR signaling.
- Ligand affinity plays a more critical role in initiating T cell activation than CD45 segregation.
- The findings challenge the necessity of CD45 exclusion for TCR signal initiation.
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