Work

CD8+ T cell recognition of cyst-derived antigen during chronic CNS infection with Toxoplasma gondii 4698

Year: 2025

Type: article

Abstract: Description Toxoplasma gondii parasites establish persistent infection within neurons by forming cysts containing latent form bradyzoites. Given the limited MHC-I expression by neurons, it was previously thought that both neurons and cysts were protected from T cell recognition. However, neurons isolated from the brains of infected mice and cyst-containing neurons were found to express MHC-I, indicating that neurons can present to T cells. Recent work suggests that a cyst-derived antigen is recognized by CD8+ T cells – but it was unclear how such antigens would get beyond the cyst wall to enter the MHC-I pathway. To explore if cyst antigens can be transported beyond the cyst wall for direct presentation by neurons, we generated a BAG1-GRA6-SIINFEKL (BAG1-GRA6) parasite line in which there is bradyzoite-specific expression of the SIINFEKL T cell epitope linked to GRA6, a secreted dense granule protein hypothesized to be transported across the cyst wall. BAG1-GRA6 antigen was detected within the cytoplasm of in-vitro infected cells, indicating that cyst antigens can get beyond the cyst wall. To determine if the BAG1-GRA6 antigen is encountered by T cells within the brain, TCR reporter Nur77-GFP-OT-Is were transferred into and then recovered from the brains of BAG1-GRA6-infected mice. A proportion of OT-Is were found to be Nur77-GFP+, indicating that these T cells recognized cyst antigen within the site. Future studies will determine the identity of the cell(s) presenting cyst antigen. Funding Sources NIH 5-R01-AI-157247-04 NIH T32 CA009140 Topic Categories Neuroimmunology (NEUR)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.2340