Location of the CD8 T Cell Epitope within the Antigenic Precursor Determines Immunogenicity and Protection against the Toxoplasma gondii Parasite

• DOI: 10.1371/journal.ppat.1003449
• Publication Date: 2013-07-16T19:48:34Z
• Authors: Virginie Feliu; Virginie Vasseur; Harshita S. Grover; H. Hamlet Chu; Mark J. Brown; Jeremy Wang; Jon P. Boyle; Ellen A. Robey; Nilabh Shastri; Nicolas Blanchard
• Keywords: Immunodominance; Intracellular parasite

CD8 T cells protect the host from disease caused by intracellular pathogens, such as Toxoplasma gondii (T. gondii) protozoan parasite. Despite complexity of T. proteome, cell responses are restricted to only a small number peptide epitopes derived limited set antigenic precursors. This phenomenon is known immunodominance and key effective vaccine design. However, mechanisms that determine immunogenicity hierarchy parasite antigens not well understood. Here, using genetically modified parasites, we show burden controlled immunodominant GRA6-specific response but subdominant GRA4- ROP7-derived epitopes. Remarkably, optimal processing were determined location epitope at C-terminus GRA6 precursor. In contrast, could be explained affinity for MHC I molecule or frequency precursors in naive animals. Our results reveal molecular requirements presentation an antigen eliciting protective cells.