Peer-Reviewed Publication
Signal Transduct Target Ther2026;11(1)July 16, 2026Journal Article
A cell-based kinetic framework enables TCR specificity prediction.
Martin Culka1,2, Jonathan Desponds3,4, Jeanne Cheung3,5, Mayra Cruz Tleugabulova3, Shirley Ng Palace3, Martine Darwish3, Roman A Smirnov6,7, Evgeniy Tabatsky8, Geraldine Strasser3,9, Andrey S Shaw3, Ira Mellman3, Andrei Chernyshev10, Darya Orlova11,12
1Department of Systems Biology, Columbia University, New York, NY, USA.
2Antiverse Czech Republic, Prague, Czech Republic.
3Genentech, South San Francisco, CA, USA.
4Servier - Symphogen, Ballerup, Denmark.
5Xaira Therapeutics, South San Francisco, CA, USA.
6Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
7McDonnell Genome Institute, Washington University, St. Louis, MO, USA.
8Couloir Bio Inc., Los Altos, CA, USA.
9Calico Life Sciences, South San Francisco, CA, USA.
10Voevodsky Institute of Chemical Kinetics and Combustion SB RAS, Novosibirsk, Russia.
11Genentech, South San Francisco, CA, USA. dyorlova@gmail.com.
12Couloir Bio Inc., Los Altos, CA, USA. dyorlova@gmail.com.
Abstract
The ability to predict T-cell receptor (TCR) specificity from sequences could transform immunotherapy, vaccine development, and our understanding of immune recognition. However, progress has been shaped by "edge cases", in which specificity appears to be captured by simplified descriptors, such as sequence motifs or correlations between binding affinity and functional activation. Although informat…
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