Fidelity of T Cell Activation Through Multistep T Cell Receptor ζ Phosphorylation

Abstract

The T cell receptor (TCR) αβ heterodimer interacts with its ligands with high specificity, but surprisingly low affinity. The role of the ζ component of the murine TCR in contributing to the fidelity of antigen recognition was examined. With sequence-specific phosphotyrosine antibodies, it was found that ζ undergoes a series of ordered phosphorylation events upon TCR engagement. Completion of phosphorylation steps is dependent on the nature of the TCR ligand. Thus, the phosphorylation steps establish thresholds for T cell activation. This study documents the sophisticated molecular events that follow the engagement of a low-affinity receptor.