Figure 4.
Cell proliferation response to co-incident SARS-CoV-2 infection associated with expansion of TCR clones enriched for SARS-CoV-2-reactive TCRs
(A) Enumeration of expanded TCR α chain abundance (per million total sequences) in non-infection controls and samples from infected individuals stratified by time from first positive PCR. Individual data points are shown with violin plots depicting median, IQR, and frequency distributions (∗FDR < 0.05 by Kruskal-Wallis test for each group compared with NIC).
(B and C) Correlation of (B) CCND1 module and (C) STAT1 module with TCR α chain sequences (log2 per million sequences). Regression lines are shown in red, with R and p values for Spearman rank correlations.
(D) The dynamics of in-vivo-expanded TCRs (counts per million TCRs) identified as SARS-CoV-2 reactive in VDJdb, displayed as a heatmap in which each row is an individual TCR (α or β gene, right-hand key) from individual participants (left-hand key). NA, no sample available; ND, not detected in sample.
(E) Number of TCR sequences (α and β genes) annotated for SARS-CoV-2, cytomegalovirus (CMV), and Epstein-Barr virus (EBV) in VDJdb matching either expanded or unexpanded TCR sequences from individuals with SARS-CoV-2 infection, giving the odds ratio (OR±95% CI, Fisher’s exact test) for enrichment of antigen-specific TCR sequences in each case.
(F) Number of SARS-CoV-2-specific TCRs in VDJdb for which the reported HLA restriction (HLA A1 or HLA A2) matches the HLA haplotype of the individual in which the expansion was observed. The number is compared with the expected number of HLA matches if HLA allocation was random, and these numbers are used to derive the OR (±95% CI, Fisher’s exact test).
(G) Number of ex vivo SARS-CoV-2 peptide-reactive TCR sequences (α and β genes) among expanded and unexpanded TCR sequences from individuals with SARS-CoV-2 infection, giving the OR (±95% CI, Fisher’s exact test) for enrichment of virus-specific TCR sequences.