Figure 3.
Cytotoxic responses and clonality of conventional and innate-like T cells in COVID-19 and SARS-CoV-2 vaccine recipients
(A and B) Graphs of cell percentages of select cytotoxic cell populations that exhibited significant differences between COVID-19-naïve donors and healthy volunteers before receiving the BNT162b2 mRNA vaccine (blue), healthy volunteers after receiving the BNT162b2 mRNA vaccine (orange) and booster (dark orange), and COVID-19 patients (red). Line graphs show percentages for given cell population per subject, per time point. Connected lines indicate repeated measurements for the same subjects. P-values for these plots are determined by an ANOVA of linear mixed models and post-hoc pairwise comparison of estimated marginal means are listed on each plot. The bars represent the upper and lower confidence intervals for the estimated marginal means for the linear model.
(C) Average per-sample scaled expression of genes associated with cytotoxic effector function from the gene set T cell mediated cytotoxicity (GO:0001913) in proliferating NK and conventional T cells. See also Figure S6.
(D) UMAP visualization of clonal T cells from healthy volunteers after receiving the BNT162b2 mRNA vaccine (left) and COVID-19 patients (right). Clonality is determined by the CDR3 sequence in TCRβ chain. Identical CDR3 sequences in at least 5 cells are colored uniquely. See also Figure S6.
(E) UMAP visualization of CD8 T cell clones (>3 cells with identical CDR3) that match reported TCRβ sequences from natural and synthetic exposure to SARS-CoV-2. While CD8 T Effector Memory and CD4 T Activated clusters overlap in UMAP space, we confirmed that all mapped clonal cells were from the CD8 T Effector Memory population. 100% amino acid sequence identity threshold was used in mapping of CDR3 region to Spike-specific reported sequences.43 See also Figure S7.
(F) UMAP visualization of clonal γδ T cells from healthy volunteers after receiving the BNT162b2 mRNA vaccine (left) and COVID-19 patients (right). Clonality is determined by the CDR3 sequence in TCRδ chain. Identical CDR3 sequences in at least 5 cells are colored uniquely. See also Figure S9.