APATRIVAP · Antigen processing and T cell recognition of intravacuolar parasites

Antigen recognition by CD8 T cells enables us to combat infectious pathogens, such as viruses and parasites. This feature represents the groundwork for vaccine efficacy. Immune surveillance is achieved by screening short peptides presented by major histocompatibility complex (MHC) class I molecules on the surface of infected cells. Recognition of foreign peptide-MHC I complexes triggers cytokine production and cytotoxicity towards the infected target. CD8 T cells are key for protection against intravacuolar parasites, likes the malaria-causing Plasmodium falciparum and a closely related parasite : Toxoplasma gondii (T. gondii). T. gondii infection can cause life-threatening encephalitis in immunocompromised individuals and severe birth defects if pregnant women get primo-infected. Yet, how the parasite antigens are degraded by the MHC I pathway and how it leads to ultimate establishment of protective CD8 T cells is poorly characterized. Here, using tools and findings obtained during my post-doctoral training in the USA, I propose to use the genetically tractable T. gondii parasites as a model to study T cell immunity to intravacuolar parasites. First, I will address the mechanisms underlying cytosolic access and processing of T. gondii antigens (aim 1). Then we will study the potential strategies used by the parasites to evade CD8 T cell recognition (aim 2). As a longer-term development, we will examine the induction of parasite-specific intestinal T cells in vivo, following oral infection (aim 3). This proposal should have a fundamental significance by revealing novel pathways of antigen processing, as well as a clinical relevance by suggesting ways to manipulate antigen processing and lead to the creation of vaccines against toxoplasmosis. This project will be undertaken in the “Immunology and Infectious diseases” department of the CPTP-INSERM U563 research centre in Toulouse, France.