Molecular Mimicry between B-Cell Epitopes and Neurodevelopmental Proteins: An Immunoinformatic Approach.

Epidemiological studies and meta-analyses have shown a strong association between high seroprevalence of () and schizophrenia. Schizophrenic patients showed higher levels of anti-Toxoplasma immunoglobulins M and G (IgM and IgG) when compared to healthy controls. Previously, in a rat model, we demonstrated that the progeny of mothers immunized with lysates before gestation had behavioral and social impairments during adulthood. Therefore, we suggested that infection can trigger autoreactivity by molecularly mimicking host brain proteins. Here, we aimed to identify the occurrence of antigenic mimicry between epitopes and host brain proteins. Using a bioinformatic approach, we predicted cell epitopes and compared them to human cell-surface proteins involved in brain development and differentiation (BrainS). Five different algorithms for B-cell-epitope prediction were used and compared, resulting in 8584 epitopes. We then compared predicted epitopes to BrainS proteins by local sequence alignments using BLASTP. immunogenic epitopes significantly overlapped with 42 BrainS proteins. Among these overlapping proteins essential for brain development and differentiation, we identified HSP90 and NOTCH receptors as the proteins most likely to be targeted by the maternally generated pathogenic antibodies due to their topological overlap at the extracellular region of their sequence. This analysis highlights the relevance of pregestational clinical surveillance and screening for potential pathogenic anti- antibodies. It also identifies potential targets for the design of vaccines that could prevent behavioral and cognitive impairments associated with pre-gestational exposure.