Stereo-selective binding of monoclonal antibodies to the poly-gamma-d-glutamic acid capsular antigen of Bacillus anthracis

•We determined the binding affinities and specificities of several murine mAbs that react with the capsule of Bacillus anthracis.•Binding of all mAbs was not solely dependent on non-directional ionic forces.•All mAbs preferentially bound γ-linked d glutamic acid over γ-linked l glutamic acid.•The murine mAb F26G3 was the most selective for γ-linked d glutamic acid.•A molecular model of mAb F26G3 shows five glutamic acid residues optimally fill the binding site and that two conformations have 30 ps lifetimes.

Bacillus anthracis is surrounded by an anti-phagocytic capsule that is entirely composed of γ-linked d-glutamic acid (γDPGA). γDPGA is required for virulence and is produced in large quantities following spore germination. We have previously described the isolation of several γDPGA-reactive mAbs. The reagents are effective in both immunoprotection and diagnostic applications. The current work was done to further investigate the specificity of γDPGA-reactive mAbs. The specificity of each mAb was characterized using surface plasmon resonance. Our results indicate that each mAb is stereoselective for binding to d-glutamic acid oligomers, but to varying degrees. In particular, mAb F26G3 is highly selective for γDPGA; alterations in stereochemistry disrupted recognition. These differences in mAb reactivity suggest that binding of γDPGA by mAb F26G3 is more specific than non-directional ionic interactions between a negatively charged antigen and a positively charged antibody.