Crystal structure of CD27 in complex with a neutralizing noncompeting antibody

Acta Crystallogr F Struct Biol Commun. 2017 May 1;73(Pt 5):294-299. doi: 10.1107/S2053230X17005957. Epub 2017 Apr 26.


CD27 is a T-cell and B-cell co-stimulatory glycoprotein of the tumor necrosis factor (TNF) receptor superfamily that is dependent on the availability of the TNF-like ligand CD70. Therapeutic approaches to treating autoimmune diseases and cancers with antagonistic and agonistic anti-CD27 monoclonal antibodies (mAbs), respectively, have recently been developed. Mouse anti-human CD27 mAb 2177 shows potency in neutralizing CD70-induced signaling; however, it does not block the binding of soluble CD70. To provide insight into the mechanism of action of the mAb, the crystal structure of the CD27 extracellular domain in complex with the Fab fragment of mAb 2177 was determined at 1.8 Å resolution. CD27 exhibits the assembly of cysteine-rich domains characteristic of the TNF receptor superfamily. The structure reveals a unique binding site of mAb 2177 at the edge of the receptor molecule, which allows the mAb to sterically block the cell-bound form of CD70 from reaching CD27 while leaving the ligand epitope clear. This mode of action suggests a potential dual use of mAb 2177 either as an antagonist or as an agonist.

Keywords: CD27; antibodies; crystal structure; cysteine-rich domain; epitopes; tumor necrosis factor.

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Antibodies, Monoclonal / chemistry*
  • Antibodies, Monoclonal / genetics
  • Antibodies, Neutralizing / chemistry*
  • Antibodies, Neutralizing / genetics
  • Antigen-Antibody Complex / chemistry*
  • Antigen-Antibody Complex / genetics
  • Baculoviridae / genetics
  • Baculoviridae / metabolism
  • Binding Sites
  • CD27 Ligand / chemistry*
  • CD27 Ligand / genetics
  • CD27 Ligand / immunology
  • Cloning, Molecular
  • Crystallography, X-Ray
  • Gene Expression
  • Genetic Vectors / chemistry
  • Genetic Vectors / metabolism
  • HEK293 Cells
  • Humans
  • Immunoglobulin Fab Fragments / chemistry*
  • Immunoglobulin Fab Fragments / genetics
  • Ligands
  • Mice
  • Models, Molecular
  • Protein Binding
  • Protein Conformation, beta-Strand
  • Protein Interaction Domains and Motifs
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Sequence Alignment
  • Sf9 Cells
  • Spodoptera
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / chemistry*
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / genetics
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / immunology


  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antigen-Antibody Complex
  • CD27 Ligand
  • CD70 protein, human
  • Immunoglobulin Fab Fragments
  • Ligands
  • Recombinant Fusion Proteins
  • Tumor Necrosis Factor Receptor Superfamily, Member 7