Abstract
Comparing mammalian proteomes for molecular mimicry with infectious pathogens highlights the highest levels of heptapeptide sharing between pathogens and human, murine, and rat proteomes, while the peptide sharing level is minimal (or absent) with proteomes from nonhuman primates such as gorilla, chimpanzee, and rhesus macaque. From the medical point of view, the data might be useful to clinicians and vaccinologists to develop and evaluate immunomodulatory and immunotherapeutic approaches. As a matter of fact, primates seem to be unreliable animal models for revealing potential autoimmune events in preclinical testing of immunotherapies. In terms of genomics, the scarce or absent peptide sharing between pathogens and primates versus the massive peptide sharing existing between pathogens and humans lets foresee mechanisms of pathogen sequence insertion/deletion/alteration that have differently operated in mammals over evolutionary timescales. Why and how the human genome has been colonized by pathogen sequences and why and how primates escaped such a colonization appears to be the new scientific challenge in our efforts to understand not only the origin of Homo sapiens but also his autoimmune diseasome.
Highlights
Molecular mimicry and the consequent potential cross-reactivity following infections have been repeatedly described in humans.[1,2,3,4,5,6,7,8,9,10,11,12] Such cross-reactivity is not evident in experimental infections of primates.[13]
If it is true that molecular mimicry between infectious agents and human proteins contributes to or causes cross-reactions and postinfection autoimmune pathologies, the human proteome should be characterized by different levels/patterns of molecular mimicry versus pathogens when compared with the proteomes of nonhuman primates
Pathogen proteomes were dissected into heptapeptides offset by one residue, and each pathogen heptapeptide was analyzed for occurrences within proteomes from the following organisms: Homo sapiens (9606); gorilla, Gorilla gorilla gorilla (9595); chimpanzee, Pan troglodytes (9598); and rhesus macaque, Macaca mulatta (9544)
Summary
Molecular mimicry and the consequent potential cross-reactivity following infections have been repeatedly described in humans.[1,2,3,4,5,6,7,8,9,10,11,12] Such cross-reactivity is not evident in experimental infections of primates.[13]. If it is true that molecular mimicry between infectious agents and human proteins contributes to or causes cross-reactions and postinfection autoimmune pathologies, the human proteome should be characterized by different levels/patterns of molecular mimicry versus pathogens when compared with the proteomes of nonhuman primates. According to this rationale, this study comparatively analyzed primate and human proteomes for peptide sharing with pathogens by using heptapeptides as immunobiological units.[20–22]. This study comparatively analyzed primate and human proteomes for peptide sharing with pathogens by using heptapeptides as immunobiological units.[20–22] Analyses were expanded to other mammalian species that are used in research laboratories
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