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Sabotaging TCR signaling—LAG3 interferes with the CD3ε–LCK interaction

Gina J. Fiala¹ , Wolfgang W. Schamel^1,2,*

¹Signalling Research Centres BIOSS and CIBSS, and Department of Immunology, Insitute of Biology III, Faculty of Biology, University of Freiburg, Freiburg im Breisgau, Germany
²Centre for Chronic Immunodeficiency (CCI), and Centre for Cell and Gene Therapy Freiburg (CGF), Medical Centre Freiburg and Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany
* Correspondence: Wolfgang W. Schamel(wolfgang.schamel@biologie.uni-freiburg.de)

T cell activation occurs when the TCR–CD3 complex binds pMHC, leading to recruitment of the kinase LCK to CD3ε, which triggers CD3 phosphorylation by LCK and downstream signaling. The inhibitory receptor LAG3 dampens TCR–CD3 signaling and T cell responses; two recent studies clarified its inhibitory mechanisms and therapeutic applications in cancer and autoimmunity.

https://doi.org/10.1038/s41422-025-01168-7

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