Intracellular calcium dynamics are predictive of T cell receptor affinity for cognate antigen

Le résumé fourni par la source

The strength of antigen recognition by the T cell receptor (TCR) dictates T cell fate and function. However, existing biochemical, biophysical, and cell-based approaches to quantify TCR avidity for cognate antigen are limited in their ability to scale to single-cell analysis across polyclonal T cell populations. To address this limitation, we propose a microscopy-based method based on intracellular calcium (Ca2+) oscillations, an early functional readout of TCR engagement, to predict TCR avidity. We show that the avidity of the TCR interaction with cognate antigen influences the dynamics of intracellular Ca2+ fluctuations as well as cell migration patterns. Leveraging these insights, we trained a deep learning model to predict the affinity of individual naive CD8 T cells for an antigen of interest following activation. We validated its performance across multiple TCRs and model antigens while demonstrating its application in a polyclonal T cell repertoire. This study establishes intracellular Ca2+ dynamics as a functional biomarker for high-throughput, single-cell prediction of antigen avidity using machine learning approaches.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.