Figure 4. T-cell receptor (TCR) neighborhoods have higher density among TCRs that have been experimentally enriched for antigen-specific T cells compare to unenriched repertoires.
TCR β-chains from (A) a peptide–major histocompatibility complex (MHC) tetramer-enriched subrepertoire (n = 247), (B) a MIRA peptide stimulation-enriched subrepertoire (n = 497), or (C) an umbilical cord blood unenriched repertoire (n = 9966), and (D) synthetically generated sequences using Optimized Likelihood estimate of Immunoglobulin Amino acid sequences (OLGA; n = 10,000; Sethna et al., 2019). Within each subrepertoire, an empirical cumulative distribution function (ECDF) was estimated for each TCR (one line) acting as the centroid of a neighborhood over a range of distance radii (x-axis). Each ECDF shows the proportion of TCRs within the set with a distance to the centroid less than the indicated radius. ECDF color corresponds to the length of the complementarity determining region (CDR)3-β loop. ECDF curves were randomly shifted by <1 unit along the x-axis to reduce overplotting. Vertical ECDF lines starting at 10−4 indicate no similar TCRs at or below that radius. Percentage of TCRs with an ECDF proportion <10−3 (bottom panels), indicates the percentage of TCRs without, or with very few biochemically similar neighbors at the given radius.