Impact of Regulated Secretion on Antiparasitic CD8 T Cell Responses

• Different natural CD8 antigens dominate in susceptible versus resistant mouse strains
• Altering the secretion pattern of antigens alters immunodominance of T cell response
• Altered secretion leads to enhanced CD8 effector responses during chronic infection
• Secretory pathways are key to designing vaccines against intracellular parasites

SummaryCD8 T cells play a key role in defense against the intracellular parasite Toxoplasma, but why certain CD8 responses are more potent than others is not well understood. Here, we describe a parasite antigen, ROP5, that elicits a CD8 T cell response in genetically susceptible mice. ROP5 is secreted via parasite organelles termed rhoptries that are injected directly into host cells during invasion, whereas the protective, dense-granule antigen GRA6 is constitutively secreted into the parasitophorous vacuole. Transgenic parasites in which the ROP5 antigenic epitope was targeted for secretion through dense granules led to enhanced CD8 T cell responses, whereas targeting the GRA6 epitope to rhoptries led to reduced CD8 responses. CD8 T cell responses to the dense-granule-targeted ROP5 epitope resulted in reduced parasite load in the brain. These data suggest that the mode of secretion affects the efficacy of parasite-specific CD8 T cell responses.

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