Fig. 4: Remodeling of TCRβ repertoire following HER2 CAR T-cell infusions.

a Longitudinal homeostatic space distribution of T-cell clones from the peripheral blood (PB) categorized as hyperexpanded/large (>1% frequency of productive rearrangements), medium (0.1–1% frequency), small (more than single event, but <0.1% frequency) and rare (single rearrangement events) before and 6 weeks after the first, second and third HER2 CAR T-cell infusions. The pre-infusion sample (Pre) was obtained at 4 weeks from the prior cyclophosphamide containing chemotherapy and serves as a chemotherapy only control. b Heat map representing Morisita’s overlap index of TCRβ CDR3 rearrangements between time-matched samples from the PB and bone marrow (BM) obtained 6 weeks after the second and third CAR T-cell infusions. The overlap index has values ranging from 0 to 1 representing low to high degree of overlap, respectively. c Amino acid (AA) length distribution of the TCRβ CDR3 in peripheral blood before and 6 weeks after the first, second and third HER2 CAR T-cell infusions. d TCRβV family genes and TCRβJ family genes in the CDR3 region of peripheral blood T cells before and 6 weeks after the first, second and third HER2 CAR T-cell infusions. Only TCRβV genes with >1% of cumulative productive frequencies are represented. Complete TCRβV family gene use is provided as Supplementary Table 4. Inf infusion, L left, R right.