Mapping Plasmodium falciparum specific T cell epitopes in human liver tissue

The development of a multi-stage malaria vaccine will likely benefit from the inclusion of CD8 T cell epitopes to induce tissue-resident memory (Trm) cells in the liver. The hepatic phase of the Plasmodium falciparum (Pf) life cycle represents a bottleneck in parasite development due to the small number of parasites that successfully infect hepatocytes. T cells play an important role in anti-Plasmodium immunity. CD4 T cells provide B cell help and eliminate parasites through the production of IFNg, whereas CD8 T cells can kill infected liver cells, as demonstrated in mice and NHPs. Additional support for the role of T cells comes from unpublished human studies with late-arresting sporozoites, although the relative contribution of CD4 and CD8 cells for protection and their target epitopes is still unknown. CD8 Trm cells are ideally suited for the identification of protective Pf target epitopes. This proposal aims to determine whether Trm cells in the livers of individuals living in Pf endemic areas in India target conserved Pf antigens. If so, single-cell-based TCR discovery work will be supported to identify Pf-reactive TCRs and determine their peptide specificity and HLA restriction pattern.