Fig. 3

Analysis of T cell receptor sequence similarity within and between neurodegenerative disease groups. a Workflow for quantifying TCRαβ similarity. Clonal TCRs with unambiguous CDR3a and CDR3b sequences were retained for analysis. L-sim values were then computed between all possible combinations of TCRαβ sequences. b At left: heatmap highlighting TCR combinations with L-sim score > 0.8. At right: inset of heatmap shows three clusters of similar TCRs. Color bar represents L-sim score. c Metadata of clustered TCRs shown in b). Note the similarity of TCRs within disease groups. d Three clusters of similar TCRs identified in c) highlighted on tSNE. Clusters of TCRs overlap with CD8⁺ T cells. e TCR network displaying connections between samples with similar sequences (L-sim > 0.8) identified in b). Each node is a unique patient sample with each small circle sprouting off a node representing a unique clonal TCR. Nodes are colored by disease group; lower right heatmap shows number of similar TCRs between unique samples per disease group. f TCR network (L-sim > 0.9). g Quantification of shared motifs present in TCRβ sequences. Clonal TCRs with unambiguous CDR3b sequences were retained for analysis. The first and last two amino acids were removed from the analysis, since these regions are highly conserved. h Table of motifs of length 9. The SSLGQAYEQ motif is highlighted and metadata corresponding to patient samples is shown. i Upper: table of pathogens specific to SSLGQAYEQ motif based on search of the public McPAS-TCR database. Lower: table of SSLGQAYEQ motif-containing T cell types based on public McPAS-TCR database search