Fig. 4: Age-related changes in A2/M158+CD8+ TCRαβ repertoire.
a–e, A2/M158+CD8+ T cells were enriched by TAME followed by single-cell sorting for TCRαβ analysis. a, A 2D kernel principal-component analysis (PCA) projection of the A2/M158+CD8+ TCR landscape colored by Vα, Jα, Vβ and Jβ gene usage (left to right) for all four age groups generated by TCRdist. Encoding clone size indicated by symbol size. b, TCRdiv diversity measures of the TCRα, TCRβ or paired TCR αβ-chains. c, smoothed density profiles of neighbor distance distribution are shown for each age group. A lower distribution peak indicates more clustered A2/M158+CD8+ single TCRα, TCRβ or paired TCRαβ repertoire, average distance values for each age group are depicted within the plot. PDF, probability density function. d, TRAV and TRBV clonotype pairing per age group illustrated by circos plots. Left arch segment colors indicate TRAV usage, right outer arch colors depict TRBV usage. Connecting lines indicated TRAV–TRBV gene pairing and are colored based on their TRAV usage and segmented based on their CRD3α and CDR3β sequence, the thickness is proportional to the number of TCR clones with the respective pair. The number of sequences considered for each circos plot is shown at the right bottom. e, Frequency of high-prevalent (>2 similar TCRs within a single individual) public (shared) and private (not shared) clonotypes across different age groups. Dark red represents high-prevalent public TCR (TRAV27, TRAJ42, CDR3α GAGGGSQGNLIF, TRBV19, TRBV2–7 and CDR3β CASSIRSSYEQYF), whereas the light red are clonotypes expressing the full public TCRβ chain (TRBV19, TRBV2–7 and CDR3β CASSIRSSYEQYF) but the TCR α-chain could not be identified. Numbers in the graph represent the number of donors in which this specific high-prevalent clonotype was identified. Statistical analysis was performed using a two-sided Kruskal–Wallis test with Dunn’s correction for multiple tests. P values are indicated above the graphs. N, newborn; C, children; A, adult; OA, older adult.
