Predicting epitope specificity for an entire T cell atlas

In this study, researchers used ImmuneWatch DETECT to explore the antigen-specificity of a several TCR cluster that had been generated using 149 single-cell samples. One of these clusters was highly prevalent as it was found across 99 of 149 samples. The clones in these clusters, identified across diverse HLA types, were a mystery until ImmuneWatch DETECT predicted their specificity for riboflavin antigens presented on MR1. This insight revealed the cluster as MAIT cells, a finding later confirmed by exploring MAIT-specific markers in the gene expression data.

Why This Matters

The study highlights a shift toward a “TCR-first” approach for analysing single-cell sequencing data, which has traditionally underutilised TCR insights. By curating an atlas of 500,000 T cells spanning diseases such as melanoma, head and neck cancer, and blood cancer, the researchers addressed challenges in cell annotation, treatment-related dynamics, and public TCR clusters.

ImmuneWatch DETECT was instrumental for some of these findings, demonstrating its value as a tool for decoding TCR specificity and enabling actionable discoveries in immune research.

Read the full manuscript here:

Kerry A. Mullan et al., T cell receptor–centric perspective to multimodal single-cell data analysis.Sci. Adv. 10, eadr3196(2024). DOI: 10.1126/sciadv.adr3196

‍