Extended Data Figure 6: Generation of T cells with substantial Vβ TCR diversity from the engrafted gene-targeted HSPCs.

a, Analysis of TCR Vβ repertoire performed on PBMCs from a healthy donor. The histogram shows the frequency distribution of the different complementarity-determining region 3 (CDR3) lengths identified within the indicated Vβ families. As expected from a highly polyclonal TCR repertoire, all Vβ families display a Gaussian distribution of the CDR3 lengths. b, Frequency distribution of the different CDR3 regions measured as in a for the GFP⁺ (left) and GFP⁻ (right) T cells harvested from the transplanted C1, C5 and A4 mice from Extended Data Fig. 5c. c, Complexity score³⁶ assigned to each Vβ family for the samples shown in b. The sum of the scores for all the family is plotted in Fig. 4g. Note that all the samples analysed display similar TCR Vβ repertoire distributions, constrained for some families and more polyclonal for others, as might be expected for human T cells developed in haematochimaeric mice⁴¹, and that no significant differences are observed between the GFP⁺ and GFP⁻ cells. This finding indicates that the rate of gene targeting achieved in the transplanted stem/progenitor cells does not detectably limit the generation of a polyclonal and functional T-cell repertoire in vivo.