Public Baseline and shared response structures support the theory of antibody repertoire functional commonality

The naïve antibody/B-cell receptor (BCR) repertoires of different individuals ought to exhibit significant functional commonality, given that most pathogens trigger an effective antibody response immunodominant epitopes. Sequence-based repertoire analysis has so far offered little evidence for this phenomenon. For example, a recent study estimated the number shared (‘public’) clonotypes in circulating baseline be around 0.02% across ten unrelated individuals. However, engage same epitope, antibodies only require similar binding site structure and presence key paratope interactions, which can occur even when their sequences are dissimilar. Here, we search geometric similarity/convergence human repertoires. We first structurally profile (‘baseline’) diversity using snapshots from 41 individuals, predicting all modellable distinct structures within each repertoire. This uncovers high (much greater than random) degree structural commonality. instance, 3% common diverse individual samples (‘Public Baseline’ structures). Our approach is computational method find levels BCR commonality commensurate with epitope immunodominance could therefore harnessed more genetically distant same-epitope complementarity. then apply profiling three before after flu vaccination, detecting convergent drift indicative recognising epitopes Response’ show Antibody Model Libraries derived Public Baseline Response represent powerful basis set low-immunogenicity candidates exploitable general or target-focused therapeutic screening.