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Fig. 3 | Genome Medicine

Fig. 3

From: Exploring the pre-immune landscape of antigen-specific T cells

Fig. 3

Epitope features that affect the rearrangement probabilities of specific TCRs. a Population frequencies of TCRs specific for epitopes of different length, net partial specific volume (sixth Kidera factor), and net surrounding hydrophobicity (tenth Kidera factor). Fractions of public clonotypes (found in 5%+ of samples) are shown with population frequencies as in Fig. 2b. The association and correlation between these features and the theoretical rearrangement probabilities is highly significant: PANOVA = 10−8, Pcorr = 4 × 10−6 for length; PANOVA = 8 × 10−9, Pcorr = 10−6 for partial specific volume; PANOVA = 4 × 10−10, Pcorr = 4 × 10−8 for surrounding hydrophobicity (P values were corrected for multiple testing using the Benjamini–Hochberg method). Only epitope lengths of 8 to 11 amino acids were considered in the first subplot, as other lengths were represented by fewer than 30 TCRs. Partial specific volume and surrounding hydrophobicity were categorized into four quantiles (Q1 to Q4, from smallest to largest standardized value) according to their levels among VDJdb epitopes. See main text for details of feature selection. b CDR3 length distributions for epitope lengths of 8 to 11 amino acids. c Density plot of rearrangement probabilities for VDJdb TCRs with different CDR3 lengths. d, e Projection of epitope and CDR3 structures on a plane passing through the line connecting their C- and N-terminal residues and the center of mass of all Cα atoms. Longer epitope and CDR3 sequences result in more bulged structures. Data were obtained from a manually curated list of 125 PDB structures []. f Schematic representation of the association between CDR3 and epitope lengths and the potential consequences for TCR cross-reactivity and specificity

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