Volume 35, No 5, May 2025

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 35 Issue 5, May 2025: 324-325

RESEARCH HIGHLIGHTS

Mechano-pharmacology of T cell receptor specificity

Panyu Fei , Michael L. Dustin^*

Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK
Correspondence: Michael L. Dustin(michael.dustin@kennedy.ox.ac.uk)

As with many receptors, closely related T cell receptor (TCR) ligands can be characterized functionally as agonists, non-agonists and antagonists; changes to a single methylene group in the peptide bound to major histocompatibility complex (pMHC) on antigen-presenting cells determine these outcomes in combination with physical forces that help separate agonists from non-agonists. Qin et al. in Cell Research show that the co-receptor CD8 also contributes to this mechano-pharmacology, explaining the large dynamic range of the TCR‒pMHC‒CD8 system and dangers of self-peptide cross-reactivity inherent to engineered high-affinity TCR.

https://doi.org/10.1038/s41422-025-01105-8

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