S184. IN SILICO PREDICTION OF T-CELL-MEDIATED MOLECULAR MIMICRY IN TOXOPLASMOSIS AND SCHIZOPHRENIA

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Abstract Background Exposure to Toxoplasma gondii (TOXO) has been consistently associated with the development of schizophrenia, but the neurobiological mechanism through which this occurs is not well elucidated. Emerging data has broadly implicated the adaptive immune system as a possible pathway from TOXO infection to schizophrenia. In order to explore the hypothesis that crossreactive T cells could help mediate this relationship, we built upon the genetic analysis from our psychiatrically-enriched Ashkenazi Jewish cohort using an in silico approach to predict HLA reactivity to TOXO epitopes, with the aim of identifying host proteins that could be susceptible to T-cell-mediated molecular mimicry. Methods We used netMHCpan v4.0 to generate a library of 2182 oligopeptides from the TOXO proteome that were predicted to be strongly antigenic for individuals with HLA-C*04:01, an allele of interest since our analysis indicated that the odds ratio for TOXO infection were in the opposite direction for those with schizophrenia compared to controls. A predicted binding affinity less than 500 nM was used to identify epitopes that were likely to be biologically relevant. Epitopes identified by this approach were compared with human peptides for local sequence similarity using BLAST optimized for short peptide sequences in order to identify host proteins that could mimic TOXO antigens. Ing

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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