The self/nonself issue: A confrontation between proteomes.

Defining self and nonself is the most compelling challenge in science today, at the basis of the numerous questions that remain unanswered in the immunology-pathology-therapy debate. The generation of the antibody repertoire, the complicated scenario offered by tolerance and autoimmunity, natural auto-antibodies and their relationship to autoimmune diseases, and positive and negative selection are only a few examples of the unresolved immunological questions. In this context, we proposed that sequence similarity to the host proteome modulates antigen peptide recognition and immunogenicity. Using the available proteome assemblies of viruses, bacteria and higher vertebrates, and applying the low-similarity criterion, we are systematically defining the proteomic similarity of B-cell epitopes already validated experimentally. Here, we report further data documenting that a low similarity to the host proteome is the common property that defines the immunological "nonself" nature of antigenic sequences in cancer, autoimmunity, infectious diseases and allergy.