Fig. 8: Comparison of TCR and BCR repertoires between young and old donors before and after vaccination.

a, Schematic workflow for inferring SARS-CoV-2 antigen specificity for the CD8 T cells from young and old donors before and after vaccination using the tessa and TCRdist3 machine learning frameworks, respectively. CDR3aa, CDR3 amino acid sequence; CDR3n, CDR3 nucleic acid sequence. b, Exemplary t-distributed stochastic neighbor embedding (t-SNE) visualization of TCR clonotypes in the space of SARS-CoV-2 TCR embedding for representative young and old donors before and after vaccination. Networks containing ≥5 TCR clones are marked by colors. The same color in each panel represents that these TCRs are in the same network, and the color mapping is specific to each panel. c, Statistics of the proportion of TCR clonotype networks potentially specific to SARS-CoV-2 antigens before and after vaccination for young (n = 3) and old (n = 3) donors under the tessa machine learning framework. Data are shown as mean ± s.d. d, Same as b but for TCR clonotype visualization and projection using TCR embedding derived from literature reported S 269–277 YLQ SARS-CoV-2 epitope-specific TCRs and corresponding scRNA-seq data. e, Same as c but for TCR clonotype networks potentially specific to S 269–277 YLQ SARS-CoV-2 epitope. f, Statistics of sum of frequencies of TCRs within the radius of the centroid specific to SARS-CoV-2 antigens before and after vaccination for young (n = 3) and old (n = 3) donors under the TCRdist3 machine learning framework. Data are shown as mean ± s.d. g, Same as f but for the TCRdist3 model built with TCRs specific to S 269–277 YLQ SARS-CoV-2 epitope. h, Diversity estimation of vaccination-induced repertoire changes of CD8 T and B cells between the young and old donors. Higher value indicates greater diversity. *P < 0.05, **P < 0.01, ***P < 0.001 and NS, not significant. Wilcoxon rank-sum test (two-sided). i, Clonotype expansion of the top 40 CDR3 clonotypes for CD8 TCRβ, IgH, IgK and IgL for young and old groups before and after vaccination (7 days after the second dose).