Figure 4.

Rare endogenous CD8 T cell responses pose challenges to fusion-specific TCR identification in multiple FLC patients

(A) Summary of experiments conducted using expanded TIL and tumor samples from four FLC patients (see also Table 1). Samples were stimulated by the indicated fusion peptide prior to single-cell gene expression and paired TCR sequencing. Pie charts represent TCR clonal expansions; expanded pie charts (where present) represent the top 20 most frequent clonotypes and indicate the overall frequency of the most frequent clone (dark blue). UMAP plots highlight expression of IFNG. FLC-SJ1, 490 cells; FLC-SJ2, 5,619 cells; FLC-SJ3, 3,212 cells; FLC-SJ4, 3,016 cells.

(B) Frequency of A∗68:02-EIFDRYGEEV tetramer-positive Jurkat cells expressing SJ1 candidate fusion-specific TCRs.

(C) Normalized frequency of CD69-positive Jurkat cells expressing candidate fusion-specific TCRs from all patients in (A) (see STAR Methods for calculation).

(D) TCRdist network of 8,270 unique, paired TCRs from SJ1. Each node represents a unique TCR clonotype, and two nodes are connected by an edge when their TCRdist < 100; node size corresponds to node degree (number of neighbors). The large central cluster represents mucosal-associated invariant T (MAIT) cells. SJ1-4 and SJ1-12 TCRs are highlighted.

See also Figures S4 and S5.