The review (https://doi.org/10.1038/s41577-026-01331-0) brings together established and emerging technologies that are transforming researchers' ability to identify and analyse these rare cells at unprecedented resolution, while also examining the technical challenges and limitations of current approaches. It highlights how these methods are providing new insights into how antigen-specific T cells develop, function and respond during infection, cancer and autoimmune disease.
The authors also discuss how integrating epitope specificity, T cell receptor (TCR) usage and functional profiles across blood and tissues is reshaping our understanding of T cell immunity. They emphasise that comprehensive annotation of paired TCRαβ sequences with defined antigen specificities will be essential for advancing computational analyses and developing predictive models of T cell recognition.