Characterizing the type 2 immune response in the nematode model Heligmosomoides bakeri 3768

Abstract Description Approximately 1.5 billion people are infected with parasitic worms. The dynamics of priming, expansion, differentiation, contraction, and memory responses by helminth-specific Th2 cells remain understudied. We aim to create a CD4+ TCR transgenic mouse specific for H. bakeri, a gastrointestinal nematode, that will enable us to track antigen-specific CD4+ T cells. For this purpose, we have established H. bakeri infection in mice with a fixed TCR beta chain, termed TcliB. CD4+ T cells from TcliB mice largely use this transgenic TCR beta chain paired with a diversity of TCR alpha chains. We sorted small intestine lamina propria CD4+ T cells from both uninfected and H. bakeri-infected TcliB mice for scRNA-sequencing to determine their gene expression and TCR alpha chain usage. We observed heterogeneity among lamina propria CD4+ T cells subtypes, including several clusters of Th2 cells whose relative abundance varied upon helminth infection. TCR alpha chain sequencing identified expanded T cell clones in infected mice, with specific TCRs present in multiple mice. We are testing these TCRs for reactivity against H. bakeri antigens and will examine whether T cells expressing these TCRs expand in vivo upon infection. Insights from this project will provide novel perspectives into how a particular helminth-specific CD4+ T cell clone may take multiple polarization fates during infection, and whether T cell responses change during co-infection with other intestinal microbes. Funding Sources NIH R01AI162918 Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)