Fig. 3: Shared oligoclonal TCRαβ clonotypes on cytotoxic CD8+ Tconv in affected skin and blister fluid are absent from or unexpanded in unaffected skin.

a UMAPs for paired unaffected and affected skin and blister fluid samples from a single patient with SJS/TEN. b Differential gene expression (two-tailed Wilcoxon, Hochberg adj, p < 0.05) between keratinocytes or CD8+ Tconv cells from unaffected and affected skin (n = 1 patient with time-paired samples; unaffected skin keratinocytes, n = 331 cells; unaffected skin CD8+ Tconv, n = 142 cells; affected skin keratinocytes, n = 108 cells; affected skin CD8+ Tconv, 356 cells). Genes colored red are significantly (p < 0.05) increased (light red < 0.6 log2 fold change (log2FC), dark red > 0.6log2FC). The top 10 genes are labeled. c Top functional TCR CDR3αβ pairings and counts (Ct.) in CD8+ Tconv cells. The same top TCR clonotypes across affected samples are highlighted in gray. d Signatures of dominant TCR+ CD8+ Tconv align to the cytotoxic Tconv cluster. Expression of the top 3 dominantly-expanded TCR (black) on CD8+ Tconv cells of each sample. The number of dominant TCR+ cells aligned to CD8+ Tconv cluster 2 (control) and cluster 3 (cytotoxic) are indicated numerically. e Differential gene expression (two-tailed Wilcoxon, Hochberg adj, p < 0.05) between CD8+ Tconv expressing dominant TCRs or other TCRs in affected skin or blister fluids (n = 1 patient with time-paired samples; affected skin DomTCRNEG, 192 cells; affected skin DomTCRPOS, n = 47 cells; blister fluid DomTCRNEG, 2441 cells; blister fluid DomTCRPOS, n = 559 cells). Genes colored red are significantly (p < 0.05) increased (light red < 0.6log2FC, dark red > 0.6log2FC). The top 10 genes are labeled. Figure created using Visual Genomics Analysis Studio (VGAS)89. Source data are provided as a Source Data file. TCR, T cell receptor; Dom TCR, Dominantly-expanded TCR; MSC, Mesenchymal stromal cell; HSC, Hematopoietic stem cell; NK, Natural killer; DC, Dendritic cell; Tconv, T conventional cell; CDR3, Complementary determining region 3; Ct., count; FDR, false discovery rate; FC, fold change; Dom TCR, dominant TCRs; SJS/TEN, Stevens-Johnson syndrome and toxic epidermal necrolysis.