Pentapeptide commonality between Corynebacterium diphtheriae toxin and the Homo sapiens proteome

Cross-reactivity may affect diagnostic tests and cause harmful autoimmune reactions following immunotherapy. To predict potential cross-reactivity and search for safe immunotherapeutic approaches, we analyzed sequence identity between microbial antigens and the human proteome. Using diphtheria toxin (DT) as a model, we examined its patterns of identity with human proteins at the pentapeptide level. DT shares 503 pentapeptides with the human proteome, while only 31 pentapeptides are unique to the toxin. DT pentapeptide identity involves multiple/repeated matches in human proteins (a total of 4966 occurrences). Human proteins containing bacterial peptide matches include antigens linked to fundamental cellular functions, such as cell cycle control, proliferation, development and differentiation. The data presented in this article offer a rational basis for designing peptide-based vaccines that specifically target DT and thus eliminate the potential risk of cross-reactivity with human proteins. More generally, this study proposes a methodological approach for avoiding cross-reactivity in immune reactions.