Fig. 1. Citrullination alters antigen processing, resulting in the simultaneous generation of cryptic peptides and the destruction of previously dominant peptides.

a Log₂ enrichment of peptides from proteolytic mapping with cathepsins BSH across the primary amino acid sequence of each protein. Amino acid positions with positive values are enriched in the PAD2- or PAD4-citrullinated (cit) samples compared to the native (nat) samples, while those with negative values are reduced by citrullination. Citrulline residues are denoted by the filled blue circles on x axes. b Volcano plots representing peptides with significantly altered abundance. Vertical lines denote a fold change of 2, and the horizontal line denotes a cutoff of 0.05 for the FDR-corrected P value (q value), calculated by paired two-sided Student’s t tests. Peptides to the left or right of vertical dashed lines and above horizontal dashed line are deemed to be significantly different between the groups. Proteolytic mapping was performed in replicates of four (fibrinogen and vimentin) or six (hnRNP A2/B1).