About
A common immune evasion mechanism utilised by pathogens is the inactivation of the host immune system. The prevalent human pathogen Streptococcus pyogenes exemplifies this, by secretion of multiple enzymes which specifically modify and inactivate human IgG antibodies, which are vital in adaptive immunity. The exquisite specificity of these enzymes for human IgG has driven their clinical use in dampening unwanted immune responses, such as during organ transplantation, autoimmune disease and cancer immunotherapy. During her PhD studies, Abigail investgated the structural basis of several antibody-degrading enzymes from S.pyogenes (named IdeS, EndoS and EndoS2) binding to their human IgG Fc target, generating crystal structures of these enzyme-antibody complexes. These studies will now be utilised in further research to develop novel antibody-modulating enzymes, using a combination of structural rationale and computational protein design.