【Nature Sub-Journal】Natural mechanism leads to a 50-fold increase in T cell activation sensitivity!

This article is original from Translational Medicine Network, please indicate the source for reprinting 

Author: Jeff

Introduction: Interactions between T-cell receptors (TCRs) and peptide major histocompatibility complex (pMHC) ligands are usually mediated by non-covalent bonds

Researchers have identified a new mechanism by which T cells can respond to lower doses of antigen

#Sec9

'Accelerating' T cells

 01 

While immunotherapy is a big step forward in treating some cancers and autoimmune diseases, this type of treatment doesn't work for many patients

The team observed a previously unobserved immune interaction that had been invisible because T cell activation levels were above the threshold that normally causes these T cells to be 'deleted' from the immune system

TCR-pMHC interaction

 02

The interactions between TCR and pMHC ligands are very diverse, but the physiological TCR-pMHC interactions involving covalent bonds are unknown

Since the kinetic schooling model assumes that T-cell activation requires the TCR-pMHC complex to persist long enough to activate TCR signaling, this model is sufficient to explain why long-lived, covalently bound TCR-pMHC complexes trigger T-cell activation

T cell activation

 03 

Here, by introducing Cys substitutions into a previously described mouse TCR, we show that Cys residues at the top of CDR3α or CDR3β are sufficient to redirect T cell fate in vivo

Furthermore, by introducing amino acid substitutions in peptide epitopes, the researchers demonstrated SS bond formation between the TCR and various pMHC ligands

References:

https://medicalxpress.

Note: This article is intended to introduce the progress of medical research and cannot be used as a reference for treatment plans

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