Fig. 3: Clonal structure of the SARS-CoV-2 epitope-specific T-cell response.

a MHC-tetramer⁺ CD8⁺ cells were subjected to fluorescence-activated cell sorting (FACS) after rapid in vitro peptide-induced expansion of PBMCs from CP (n = 14), and their TCRβ repertoire was sequenced. A representative enrichment plot is shown for patient p1426, epitope ALS at TP1. Frequencies of CDR3β sequences in the MHC-tetramer^- and the MHC-tetramer⁺ populations are plotted. Red dots represent clonotypes that are strongly (>10-fold) and significantly (p < 10⁻¹², Fisher’s exact test) enriched in the MHC-tetramer⁺ population; b numbers of specific clonotypes for each epitope at TP1 (dark blue, n = 36) and TP2 (light blue, n = 25). Boxplots show the first and third quartiles with median; whiskers show 1.5 interquartile range values; c number of epitope-specific clonotypes in the CP cohort, where each dot represents a unique patient-epitope combination (medians are shown). TP1 - dark blue, n = 36 and TP2 - light blue, n = 25; d number of specific clonotypes per epitope at TP1 which exhibited an unchanged (n = 26) or decreased (n = 13) overall response at TP2; e frequency of epitope-specific clonotypes in PBMC at TP1 (dark blue) and TP2 (light blue); f Venn diagrams showing overlap between different clonotype fractions from the CP cohort; g frequency (f) of epitope-specific clonotypes in expansions performed at the two time-points. Color represents the number of clonotypes in each bin. Mann–Whitney p values are shown only where significance was reached.