Figure 1 (Key Figure): The T cell receptor (TCR) sequence as a molecular barcode and beyond.

The TCR sequence can be used as a barcode to track clonal expansion, diversity, and migration, as well as a set of features to inform T cell fate and function. The pre-immune repertoire of T cells is highly diverse at the TCR level, in which virtually all naïve T cells have a unique TCR sequence [14, 15]. With T cell activation comes clonal expansion, where an individual T cell will divide numerous times, and the TCR is heritably maintained during cell division [3]. In this way, sister clones can be tracked within or between tissues based on sharing of the TCR sequence [27–29, 36, 38, 39, 50, 51]. Additionally, the TCR also acts as a set of features that influence T cell fate and function following antigen encounter [68, 69, 71]. In the figure, T cells (which can refer to either CD4⁺ or CD8⁺ T cells) with the same color TCR are considered clones based on matching sequences. Abbreviations used: TCR = T cell receptor; LN = lymph node; Tconv = conventional CD4⁺ T cell (non-Treg), Treg = CD4⁺ regulatory T cell; pMHCI = peptide/Major Histocompatibility Class I complex. Created with BioRender.com.