Highly cross-reactive and competent effectors dominate the CD8+ T cell response in Trypanosoma cruzi infection

CD8+ T cells are key effectors in immune control of Trypanosoma cruzi infection. Within C57BL/6 mice, the T. cruzi-specific CD8+ T cell response is higly focused on several immunodominant epitopes including TSKb20. These immunodominant epitopes all elicit non-protective T cell responses that are entirely dispensable for immune control, suggesting that other, subdominant CD8+ T cells of unknown specificities might play an important role in mediating parasite control. We assessed the relative effector capacity of TSKb20 T cells compared to other responding T cells at the site of reinfection using paired scRNA and TCR sequencing to evaluate the gene expression profiles of particular T cell clonotypes. Overall design: Chronic T. cruzi-infected (336 dpi) Nur77-GFP reporter mice were reinfected in the muscle and then T cells were isolated from the site (13 days post reinfection) for assessment of their gene expression via paired scRNA-seq and TCR-seq. TSKb20 tetramer bound and TCR-activated (based on Nur77-GFP reporter expression) CD8+ T cell populations from 5 individual mice were each isolated, sorted, and then combined for library preparation.