Poster Presentation First Malaria World Congress 2018

T Cell response to an MHC-II-restricted epitope of rodent malaria. (#280)

Matthias Enders 1 2 , Hugh Reid 2 3 , Kylie Loh 2 3 , Daniel Fernandez-Ruiz 1 , Jamie Rossjohn 2 3 , Irina Caminschi 4 , Geoff McFadden 5 , Anton Coziinsen 5 , Williiam R. Heath 1 2
  1. Department of Microbiology and immunology, University of Melbourne, Melbourne, Victoria, Australia
  2. The ARC Centre of Excellence in Advanced Molecular Imaging University of Melbourne, Parkville, Victoria , Australia
  3. Infection and Immunity Program & Department of Biochemistry and Molecular BiologyClayton, Monash University , Clayton, Victoria, Australia
  4. Monahs University, Melbourne, Victoria, Australia
  5. University of Melbourne, Melbourne, VICTORIA, Australia

Malaria is a disease of many different animals including man and rodents and is caused by several different Plasmodium species. We have identified an MHC-II-restricted epitope that is expressed by both rodent and human Plasmodium species and is presented by the MHC II IAb haplotype of B6 mice. This epitope is recognized by the PbT-II transgenic line and when conjugated to an anti-Clec9A antibody is able to induce a response by PbT-II cells. This project examines the evolution of an MHC II-restricted response to this novel MHC II-restricted epitope after infection of B6 mice by various Plasmodium species. Furthermore, we characterise the protective capacity of the CD4T cell response to this specificity by using antibody-mediated Clec9A-targeting of this epitope for vaccination. In an initial step to achieve this goal, GFP-expressing PbT-II transgenic T cells were adoptively transferred into naïve B6 mice that were then infected with P. berghei ANKA (PbA) blood-stage parasites or vaccinated with Clec9A-targeted antigen. We then followed the expansion of these CD4 T cells within the spleen and liver at various times after infection. This showed that both infection and vaccination led to a large increase in PbT-II cell numbers within 7 days followed by a decline at memory time points, with vaccination superior to infection in the generation of memory. By using intravital 2-photon imaging of the liver we were also able to identify memory cells with a patrolling phenotype after natural infection or vaccination. Furthermore, using this vaccination strategy and challenging with live sporozites led to the formation of clusters of PbT-II memory T cells in the liver. Ongoing studies are examining the capacity of memory CD4PbT-II cells to provide protective immunity against malaria.