Agonist peptide inhibition by antagonist peptide during T cell activation: global or local effect on T cell
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T-cell activation is one of the key mechanisms for the generation of adaptive immunity. This process begins from the T-cell receptor (TCR) recognition of agonist ligand presented by antigen presenting cells (APC) like dendritic cells. It is known that multiple interactions between agonist ligand and TCR are required to activate a T-cell, while similar interactions between antagonist ligand and TCR would only weakly activate the T-cell. Although much is known about T-cell activation due to agonist and antagonist ligands, few experiments in the past have shown how T-cells react to both antagonist and agonist ligands at the same time; which is shown to be the case during several infections. Using a micropipette adhesion frequency assay multiple scenarios involving agonist and antagonist ligands can be simulated. Interactions that were looked at involved spatial and time differences between agonist and antagonist stimulation of the T-cell. For each type of ligand stimulation responses from at least three T cells were recorded. A one-way ANOVA or student’s t-test was used for analysis of the data for each stimulation type. Results from the experiments using local with simultaneous simulation and global stimulation proved to be significant when agonist stimulation only and agonist plus antagonist stimulation were compared, however the results from local and time delayed experiment proved to be insignificant. Both local with simultaneous presentation and global stimulation showed how the addition of antagonist stimulation can cause the T-cell exhibit a higher adhesion frequency to agonist ligand, especially with contact times under one second. When we planned those experiments we expected that antagonist ligands inhibition of agonist stimulation would be seen as effect opposite to the one observed. We expected to see the lowering of the adhesion frequency . However, local and time-delay stimulation showed a more complex behavior of T-cells in their reaction to stimulus. In the future with knowledge of these interactions it will be possible to focus in on the exact mechanism of T-cell activation modulation by antagonist ligands.