Reviewing the role of peptide rarity in bacterial toxin immunomics.

In the past decade, renewed efforts have been made toward the development of vaccines against cancers, infectious agents, autoimmune diseases, and allergies. These efforts have led to the accumulation of numerous peptide sequences experimentally validated as epitopes. However, the factors that render a peptide immunogenic and, more generally, the nature of the antigen-antibody recognition process remain unclear. Based on the hypothesis that potential epitopes correspond to rare sequences and/or structures, we analytically review the data on the molecular structure and properties of immunoreactive sequences derived from (or evoked by) Clostridium tetani, Bacillus anthracis, and C. botulinum toxins. A cohesive picture emerges when peptide motifs are absent or scarcely represented in endogenous self proteins as they define a common immune signature of bacterial toxin B-cell immune determinants. Likewise, the scientific literature also shows that the heavy chain third complementarity-determining regions (CDR3s) from antitoxin antibodies are characterized as being formed by rare peptide sequences. The present meta-analysis aims to provide a key to understanding the molecular nature of the immune recognition process and, in turn, to contribute to the development of effective and safe peptide-based diagnostic tools and vaccine applications.