Extended Data Fig. 1: Schematic summarizing T cell maturation and life-cycle.
From: Immune awakening revealed by peripheral T cell dynamics after one cycle of immunotherapy
a Pro-T cells undergo sequential somatic recombination of their T cell Receptor β (TCR) loci in attempts to generate functional TCR with unique CDR3 antigen binding regions. Cells that fail to generate a functional TCRβ at the first attempt can recombine their second TCR allele, but cells which fail to produce a functional TCR at the end of the process (crossed red box) are eliminated (β-selection) and their DNA, which encodes the CDR3 unique regions, enters the blood as circulating cell-free DNA (cfDNA). Surviving cells retain the T cell receptor excision circle (TREC) generated during TCR locus rearrangement as an episome in the nucleus. The TREC does not replicate so is diluted during subsequent cell divisions. b T cells with a functional TCR undergo positive and negative selection (± selection) for HLA and self-antigen recognition. The CDR3 DNA from T cells eliminated during this step is released into the blood. c Naive T cells enter the circulation as early thymic emigrants (ETE). d T cells primed by antigen presenting cells (APC) in the lymphatic system undergo clonal expansion, which dilutes the TREC amongst the daughter cells. e T cell homeostasis is maintained by subsequent contraction (turnover cycles), releasing further CDR3 DNA into the blood.
