Fig. 3: T-LGLL clonotypes’ TCRs share structural similarities with their non-leukemic counterpart.

a Network plots showing antigen-driven clonotypes from three selected patients with T-LGLL. Antigen drive denotes that the T-LGLL clone shares amino acid-level similarities with its non-leukemic repertoire. Each dot (a node) is a TCR clonotype, and clonotypes with shared amino acid-level similarities are connected by a line (an edge). The T-LGLL clones are highlighted with blue and the non-leukemic with red. Below each network plot are shown parts of the GLIPH2 results for the individual patient with the same color coding on the TCRs. Additional T-LGLL cases are shown in the Supplementary Fig. 9. b The presence of antigen drive (i.e., whether the largest clonotypes have shared amino acid-level similarities with the rest of the TCR repertoire) in T-LGLL (mononuclear cell [MNC]-sorted n = 17, CD8⁺-sorted n = 8), metastatic melanoma sampled from blood (SKCM, n = 29), rheumatoid arthritis (RA, n = 32), and healthy controls (HC, MNC-sorted n = 785, CD8⁺-sorted n = 38). T-LGLL patients have more antigen-driven cases than the rest of the conditions (P < 0.05, Fisher’s one-sided exact test). All samples were subsampled to the same read-depth (30,000 reads per sample). Results where the T-LGLL clone was excluded before downsampling and in which the subsampling was only done for the non-leukemic library are shown in the Supplementary Fig. 10a. c The proportion of mutated (n = 6) and wild-type STAT3 patients (n = 6) where antigen-driven or no antigen-driven clonotypes were detected in the MNC-cohort. d The evolution of antigen-driven and non-antigen-driven T-LGLL clonotypes in multiple timepoints. Individual lines correspond to individual T-LGLL clonotypes while the bolded line shows the median. P-value was calculated with two-sided Mann-Whitney test. e Flow cytometry analysis of Vβ repertoires and variant allele frequency (VAF) of STAT3 Y640F clone (located in the shrinking Vβ1 clone) are used to demonstrate T-LGLL clonal dynamics (clonal drift) in patient 1. f UMAP representation of the CD8⁺ T cells from patient 1 from two different timepoints. The left panel highlights the different clusters, and the superimposed lines correspond to predicted maturation trajectories (pseudotime) calculated with a pseudotime algorithm Slingshot. The middle panel illustrates the expanding and shrinking clones. The panel on the right highlights the previously defined cytotoxicity score in T-LGLL clonotypes.