The adaptive immune system requires an enormously diverse repertoire of antigen receptors (AgRs) on T and B cells. This diversity is generated by DNA rearrangement in each developing lymphocyte that combines randomly chosen gene segments and introduces additional variability at the junctions between segments. The distinctiveness and diversity of AgRs mean that single-cell techniques are ideal to study antigen receptor repertoires. Furthermore, AgRs are heterodimeric proteins that comprise two independently encoded protein chains that both typically determine each receptor’s antigen specificity; single-cell measurements identify the paired receptor chains in each cell.
Single-cell AgR analysis allows us to infer clonal relationships between lymphocytes and connect this to their transcriptional state. I will discuss insights that have been gained using this approach and the potential for exciting future advances that will be made possible by methods also identify each receptor’s cognate antigen. I will introduce a new, large-scale dataset that maps TCR specificity with high throughput and resolution.