A Rationally Designed TNF-α Epitope-Scaffold Immunogen Induces Sustained Antibody Response and Alleviates Collagen-Induced Arthritis in Mice
(A) The crystal structure of the mTNF-α from PDB 2tnf. The neutralizing epitope-containing peptide was green colored. (B) The crystal structure of DTT from PDB 1MDT. The transplantation site is highlighted in green. The position of Th epitopes is indicated in red. The position of conformational perturbation in DTNF2, 5, 6 is colored in yellow, and that in DTNF4 is colored in blue. (C) The circular dichroism spectra of DTT and DTNF proteins. (D) Generation of epitope-scaffold DTNF proteins. Two to eight amino acid residues of DTT at indicated positions (red hyphens) were replaced by the TNF-α epitope peptide (in black and bold). TD (Å) stands for the interatomic distance between Valine 80 to Serine 96 or Valine 97 of TNF-α. DD (Å) stands for the interatomic distance between end residues of the replaced segment.