Fig. 5. Intrinsic bias in human TCR repertoire formation and selection.

(A) Heat map showing the proportion of each TCRβ V, D, and J gene segment present at progressive stages of T cell development. Gene segments are positioned according to genomic location. (B) Same scheme as in (A) applied to TCRα V and J gene segments. Although there is a usage bias of segments at the beginning of development, segments are evenly used by the late developmental stages, indicating progressive recombination leading to even usage of segments. (C and D) Schematics illustrating a hypothetical chromatin loop that may explain genomic location bias in recombination of TCRβ locus (C) and the mechanism of progressive recombination of TCRα locus leading to even usage of segments (D). (E) Principal components analysis plots showing TRBV or TRAV and TRAJ gene usage pattern in different T cell types. Arrows depict T cell developmental order. For TRBV, there is a strong effect from beta selection, after which point the CD4⁺ and CD8⁺ repertoires diverge. The development for TRAV+ TRAJ is more progressive, with stepwise divergence into the CD4⁺ and CD8⁺ repertoires. (F) Relative usage of TCRα V and J gene segments according to cell type. The z-score for each segment is calculated from the distribution of normalized proportions stratified by the cell type and sample. P value is calculated by comparing z-scores in CD4⁺ T and CD8⁺ T cells using t test, and false discovery rate (FDR) is calculated using Benjamini-Hochberg correction: *P < 0.05, **FDR < 10%. Gene names and asterisks are colored by significant enrichment in CD4⁺ T cells (blue) or CD8⁺ T cells (orange).