Peptide‐induced T cell receptor down‐regulation on naive T cells predicts agonist/partial agonist properties and strictly correlates with T cell activation

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Abstract
Recent experiments defining T cell agonists, partial agonists and antagonists have suggested that the T cell can discriminate between subtle differences in interactions leading to T cell activation. To further understand the complexities of T cell activation, we have analyzed the requirements for the induction of a variety of effector functions using naive T cells and a variety of altered peptide ligands. Using a strong agonist peptide, massive T cell receptor (TCR) down‐regulation correlated with a wide range of effector functions that were all induced above the same threshold peptide concentration. Interestingly, the kinetics of TCR down‐regulation correlated with the concentration of the peptide, whereas the maximal degree of TCR down‐regulation correlated with the induction of all monitored effector functions. A selected group of altered peptide ligands was also examined that were able to render target cells susceptible for lysis by effector cytotoxic T lymphocytes. The extent of TCR down‐regulation induced by these peptides corresponded to the induction of a subset of effector functions. These studies have shown that the extent of TCR down‐regulation defines the strength of TCR‐mediated “signal 1” which correlates with the spectrum of effector functions activated within the T cell. Thus, activation of different T cell functions requires the triggering of distinct numbers of TCR. The different parameters that influence TCR down‐regulation define important distinctions between our results and previously reported findings with T cell clones and may outline decisive parameters for the consequences of T cell activation in vivo.