Population-specific design of de-immunized protein biotherapeutics - Fig 2

<p>(A) Immunogenicity screening for three DRB1 alleles (DRB1*15:01, DRB1*03:01 and DRB1*07:01) with TEPITOPEpan. All peptides who’s predicted binding affinity fell into the 95% percentile of TEPITOPEpan’s score distributions have been considered epitopes. The blue regions depict the cumulative number of predicted epitopes per position and the orange regions depict the EC cumulative summary scores of top 70 ECs. Six immunogenic regions can be identified based on the <i>in silico</i> screening, with region 2,321 to 2,340 having the highest number of overlapping epitopes (9 out of 16 predicted epitopes) and was thus chosen as de-immunization target. It is comprised of the highest evolutionary coupling pairs. (B) The tertiary structure of Factor VIII’s C2 domain of with highlight immunogenic region selected for de-immunization redesign in blue. (C) The tertiary structure of Factor VIII’s C2 domain with marked top eight EC (red spheres) that coincide with the identified immunogenic region (blue).