Separate signaling events control TCR downregulation and T cell activation in primary human T cells.

ABSTRACT:

Introduction

T-cell antigen receptor (TCR) interaction with cognate peptide:MHC complexes trigger clustering of TCR:CD3 complexes and signal transduction. Triggered TCR:CD3 complexes are rapidly internalized and degraded in a process called ligand-induced TCR downregulation. Classic studies in immortalized T-cell lines have revealed a major role for the Src family kinase Lck in TCR downregulation. However, to what extent a similar mechanism operates in primary human T cells remains unclear.

Methods

Here, we developed an anti-CD3-mediated TCR downregulation assay, in which T-cell gene expression in primary human T cells can be knocked down by microRNA constructs. In parallel, we used CRISPR/Cas9-mediated knockout in Jurkat cells for validation experiments.

Results

We e

SUBMITTER: van der Donk LEH 

PROVIDER: S-EPMC7860602 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature