Does peptidome mimicry shape host-parasite coevolution?

The peptidome mimicry hypothesis (PMH) builds on the principle that vertebrate immunity recognizes peptides absent from the host proteome. It extends this idea to predict host-parasite coevolution outcomes, systematic 'missing peptides', the narrow host specificity of many parasites, and the higher susceptibility of some interspecies hybrids to infection. PMH proposes that long-term coevolution reduces parasite peptide vocabularies and drives convergence toward host repertoires - a pattern that can help to infer a parasite's original host. For example, analyses of SARS-CoV-2 peptide vocabularies have been used to reconstruct the virus's likely host-switching history. Beyond theory, PMH provides an independent and effective way to nominate immunogenic peptide targets for vaccine design, complementary to existing prediction methods.