Kinetic proofreading through the multi-step activation of the ZAP70 kinase underlies early T cell ligand discrimination.

ABSTRACT: T cells recognize a few high-affinity antigens among a vast array of lower affinity antigens. According to the kinetic proofreading model, antigen discrimination properties could be explained by the gradual amplification of small differences in binding affinities as the signal is transduced downstream of the T cell receptor. Which early molecular events are affected by ligand affinity, and how, has not been fully resolved. Here, we used time-resolved high-throughput proteomic analyses to identify and quantify the phosphorylation events and protein-protein interactions encoding T cell ligand discrimination in antigen-experienced T cells. Although low-affinity ligands induced phosphorylation of the Cd3 chains of the T cell receptor and the interaction of Cd3 with the Zap70 kinase as strongly

SUBMITTER: Voisinne G 

PROVIDER: S-EPMC9477740 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature