Figure 4. High-throughput epitope screening demonstrates tumor antigen specificity in KIR+CD8+ T cell clonotypes.
A) Experimental design of epitope screening platform to identify TCR specificity using ten amino acid peptide sequences (10-mer) and major histocompatibility complex hybrid molecules (MCR). B) Table summarizing KIR+CD8+ T cell clonotype specificity from the MCR screen. C) Flow cytometry plots of responding MCR reporter cells (NFAT+) when co-cultured with 16.A2 cells carrying T cell receptors derived from KIR+CD8+ T cells or controls. D) Conserved KIR+CD8+ gene signature expression in tumor CD8+ T cells, grouped by KIR+CD8+ T cell clonotypes with demonstrated MCR reactivity (TCR2328, TCR2409, TCR2647), other KIR+CD8+ T cells, or KIR−CD8+ T cells. Between group differences are measured by Wilcoxon matched-pairs signed rank testing (p < 0.05, **** p < 0.001). E) UMAP dimensionality reduction plot of all CD8+ T cells split by the tissue of origin with KIR+CD8+ T cell clonotypes with demonstrated MCR reactivity (TCR2328, TCR2409, TCR2647) highlighted.