Severe murine schistosomiasis results from disruption of the modulation of anti-egg CD4 T cell response by immunodominance of a single egg epitope

This study exploits the consistent correlation between immunodominance of the major egg antigen Sm-p40234-246, a robust Th1/Th17 anti-egg CD4 response and severe liver immunopathology in experimental murine schistosomiasis as an experimental platform to analyze how different degrees of immunodominance affect CD4 modulation and disease outcome. The results show that strong immunodominance of a restricted egg epitope repertoire skews CD4 modulation towards a pathogenic Th1/Th17 pro-inflammatory response and that neutralizing this immunodominance generates an opposite and restorative effect. These results identify immunodominance as an important pathogenic component that influences CD4 modulation in experimental murine schistosomiasis and can be manipulated to treat this and maybe other CD4 mediated diseases. SummaryAntigen informed CD4 modulation determines how efficiently the immune system neutralizes a threat; however, this process and its components are not fully comprehended. This study analyzes immunodominance as one component able to disrupt CD4 modulation and turn pathogenic an otherwise healthy immune response.