10. Kreiter, S. et al. Mutant MHC class II epitopes drive therapeutic immune responses to cancer. Nature 520, 692–696 (2015). ac –10–505 –5 05 UMAP1UMAP2CD8 CD40LG CD4 CCL4 CD8 Regulator y T cell CCL4L2 CD8 Prolife rating T cell Interf eron-associated CD8 CISH CD8 GNLY CD8 RGS13 CD8 KLRC1 CD8 IL10 CD4/CD8 FGFBP2 CD8 CRTAM CD8 CXCL13 CD4 /uni03B3/uni03B4 T cellb 300 200 100 –10–505 –5 05 UMAP1UMAP2 012345 CD8CD40LG CD4CCL4 CD8Regulatory T cellCCL4L2 CD8Proliferating T cellInterferon-associated CD 8CISH CD8GNLY CD8RGS13 CD8KLRC1 CD8IL10 CD4/CD8FGFBP2 CD8CRTAM CD8CXCL13 CD4/uni03B3/uni03B4 T cell 12345678 91 01112131415 Top 10 CD8+ TCRs Percentage0 20 40 60Negative control IDH1(R132H) CMV/AdV CMV/AdV PBMCsDCs only LILs only40 20 0ELISPot assay (IFN spots per 6 × 104 LILs) d e RLU CD3/CD28 IDH1(R132H) Negative contro l05,00010,00015,00020,000100,000150,000200,000 Expression CXCL13 CD4 Top 5 CD4+ TCRsTCR ID Fig. 4 | Molecular T cell phenotype of IDH1-vac-associated PsPD. a, IFNγ ELISpot counts of LILs from PsPD of patient ID08 at visit 07 after ex vivo stimulation with indicated reagents (see Methods). Peripheral blood mononuclear cells (PBMCs) stimulated with cytomegalovirus and adenovirus (CMV/AdV) peptides were used as positive assay control. Data shown as individual values and the mean of three technical replicates (for negative control, IDH1(R132H)). Technical unicates for CMV/AdV, dendritic cells (DCs) only, LILs only, CMV/AdV PBMCs. b , UMAP plot depicting molecular clusters defined by single-cell transcriptome of LILs ( n = 16,720 cells) from PsPD of patient ID08. c , CXCL13 expression in LILs from PsPD of patient ID08 within clusters as in b . d, Bubble plot mapping top TCR clones in CD4 + and CD8+ T cells defined by single-cell TCR sequencing onto transcriptomic clusters defined in b. e, T cell activation measured by luciferase NFAT reporter assay after overexpression of a top-five CD4 + TCR (TCR14 in d ) in human Jurkat T cells and co-culture with peptide-loaded autologous PBMCs. Data depicted as individual values and the mean of three technical replicates.