Robustness of ligand discrimination in the presence of receptor
crosstalk. There are two sources of variability in the number of TCRs
fully activated by ligand as discussed in the text. Runs of the same
simulation with different random-number seeds were done to estimate the
variability in numbers of TCRs that are fully activated. The results
are expressed as the mean ± standard deviation of 25 experiments.
There is a clear demarcation between optimal and suboptimal ligands
that depends on the T cell activation threshold. For example, if the
threshold for cell activation is set at a high value (e.g., 80% of TCR
fully activated), the T cell can distinguish its optimal ligand from
one whose koff varies by only a factor of 3.
With less stringent thresholds (e.g., 40% of TCR fully activated), the
T cell may be activated with high concentrations of this ligand but
never by a ligand with a koff of 10 ×
kopt.