Presented by

Dr. Johan Malmstrom

A highly complex pool of Immunoglobulin G (IgG) antibodies circulates in plasma that play an important role in the defense against bacteria. Such circulating IgG repertoires can contain a subset of protective IgG clones that contribute to a successful and sustained immune response. So far, detailed characterization of the circulating IgG repertoire and its relevance for immunity has remained elusive. Here, we demonstrate a structural proteogenomics workflow to decipher the properties of circulating antibody repertories relating to immunity against bacteria and viruses. The workflow combines large-scale B cell receptor sequencing, quantitative mass spectrometry and de novo protein sequencing to quantify the circulating antibody repertoire and its glycan modifications in convalescent sera and in animal models of infection. Furthermore, the method supports structural modelling of immune complexes using a combination of affinity-purification mass spectrometry, cross-linking mass spectrometry and structural modelling. Using these technical developments, we provide a time-resolved systems wide view of the maturation of the circulating antibody response and the targeted epitopes after immunization using the M1 protein from Streptococcus pyogenes. The work has also generated a compendium of recombinantly produced monoclonal antibodies for functional characterization that can be explored as therapeutic treatment candidates.